Gene expression profiling based identification of genomic signatures of multiple myeloma and uses thereof

ABSTRACT

Monoclonal gammopathy of undetermined significance can progress to multiple myeloma. Applying significance analysis of microarrays, 52 genes, involved in important pathways related to cancer, were differentially expressed between plasma cells from healthy subjects and patients with stringently defined monoclonal gammopathy of undetermined significance/smoldering multiple myeloma and symptomatic multiple myeloma. Unsupervised hierarchical clustering of 351 multiple myeloma and 44 cases of monoclonal gammopathy of undetermined significance and 16 cases of multiple myeloma with a monoclonal gammopathy of undetermined significance history, created two major cluster branches, one containing 82% of the monoclonal gammopathy of undetermined significance cases and 28% of the multiple myeloma, termed monoclonal gammopathy of undetermined significance-like multiple myeloma. Using the same clustering approach on an independent cohort of 213 cases of multiple myeloma revealed 27% with monoclonal gammopathy of undetermined significance-like multiple myeloma which, despite a lower incidence of complete remission, was associated with low-risk clinical and molecular features and superior survival. The monoclonal gammopathy of undetermined significance-like multiple myeloma signature was also seen in patients surviving more than 10 years after autotransplant.

CROSS REFERENCE TO RELATED APPLICATION

This non-provisional application claims benefit of provisional application U.S. Ser. No. 60/847,220 filed on Sep. 26, 2006 now abandoned.

FEDERAL FUNDING LEGEND

This invention was produced using funds under grant no. CA55819 and CA97513 from the National Institutes of Health. Accordingly, the Federal government has certain rights in this invention.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention generally relates to the field of cancer research. More specifically, the present invention relates to the use of gene expression profiling to identify genomic signatures specific for benign monoclonal gammopathy of undetermined significance present in multiple myeloma useful for predicting clinical outcome and survival.

2. Description of the Related Art

Multiple myeloma is a prototypical clonal B-cell malignancy with a terminally differentiated plasma cell phenotype. According to longitudinal follow-up of residents of Olmsted County, there is a 1% annual rate of progression to multiple myeloma from monoclonal gammopathy of undetermined significance. This clinically benign condition, with distinct neoplastic features such as aneuploidy, increases in frequency with advancing age reaching 5.3% in persons 70 yr and older. Although the median age is approximately 70 yr, multiple myeloma has been diagnosed in teenagers with clinical features and clinical course resembling those of the elderly. Family clusters of multiple myeloma have also been reported, but exposure to chemical and physical carcinogens is generally considered etiological in multiple myeloma; however Human herpesvirus 8 infection of dendritic cells could not be confirmed. In the case of the nuclear fall-out from the atomic bombs, a long latency phase of 15 to 20 years passed before an increase in multiple myeloma incidence was documented in Japan. Thus, it is plausible to assume that younger patients are likely to develop multiple myeloma more acutely while a smoldering clinical course has been frequently documented to precede the onset of symptomatic multiple myeloma in the elderly. Smoldering multiple myeloma can be considered as an advanced phase of monoclonal gammopathy of undetermined significance; even at the time of progression, smoldering multiple myeloma-evolved multiple myeloma usually lacks osteolytic lesions or other cardinal features of symptomatic multiple myeloma. Multiple myeloma remains hypo-proliferative with a long life span of malignant B-cells that assumes high-grade proliferative features only in the terminal phase, from which all human multiple myeloma cell lines have been derived. The majority of genetic lesions typical of multiple myeloma are already present at the monoclonal gammopathy of undetermined significance stage.

While these genetic abnormalities can only be detected in interphase cells in monoclonal gammopathy of undetermined significance, their detection by metaphase karyotyping in one-third of cases with multiple myeloma reflects an increased mitotic activity (possibly reflecting the ability of cells to proliferate outside the confines of the bone marrow milieu) and confers an adverse prognosis. While gene expression profiling of CD138-selected cells from bone marrow aspirates can discern between plasma cells from normal subjects and those from patients with multiple myeloma, it has been difficult to distinguish between plasma cells from multiple myeloma and monoclonal gammopathy of undetermined significance.

Although, monoclonal gammopathy of undetermined significance progression to multiple myeloma is reported to occur at a very low annual frequency (˜1%), little is known about the proportion of patients whose multiple myeloma has evolved from this precursor condition. The prior art is deficient in methods of identifying these distinct and prognostically relevant clinical subgroups of multiple myeloma. The present invention fulfills this long-standing need and desire in the art.

SUMMARY OF THE INVENTION

The present invention is directed to a method of gene expression profiling to identify genomic signatures specific for a disease by hybridization of nucleic acid obtained from normal individuals, individuals diagnosed with monoclonal gammopathy of undetermined significance and individuals diagnosed with multiple myeloma, with a DNA microarray and performing comparative analysis on data thus obtained where the analysis identifies specific genomic signatures for said disease.

The present invention is further directed to a method of predicting clinical outcome and survival of an individual, based on the genomic signature of multiple myeloma and monoclonal gammopathy of undetermined significance, its precursor form. The genomic signature is identified by gene expression profiling as discussed supra. The data obtained from the gene expression profiling in said individual is subjected to significance analysis of microarray and unsupervised hierarchical clustering analysis. This analysis classifies subsets of multiple myeloma as monoclonal gammopathy of undetermined significance-like multiple myeloma (MGUS-L MM), non-monoclonal gammopathy of undetermined significance-like multiple myeloma (non-MGUS-L MM) or multiple myeloma-like monoclonal gammopathy of undetermined significance (MM-L MGUS), thereby predicting clinical outcome and survival of the individual. Furthermore, the present invention teaches a method of correlating genomic signatures of multiple myeloma to the molecular classification of the disease to identify subsets of disease evolved from its precursor form, monoclonal gammopathy of undetermined significance or smoldering multiple myeloma.

The present invention is further directed to a method of predicting, clinical outcome and survival in an individual diagnosed with multiple myeloma or relapsed multiple myeloma by correlating the gene expression signature of multiple myeloma with amplification of gene copy number on various chromosomes, where the correlation predicts the clinical outcome and survival of said individual. Furthermore, the present invention is directed to a method of selecting treatment for an individual diagnosed with a disease, by identifying a specific genomic signature for the disease, based on gene expression profiling, to determine a treatment strategy for the disease.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. Expression patterns of 52 genes differentially expressed in plasma cells of normal donors and subjects with monoclonal gammopathy of undetermined significance. Two-dimensional unsupervised hierarchical cluster analysis of 52 genes (rows) in CD138-enriched plasma cells from 22 healthy donors (normal plasma cells, NPC) and 24 monoclonal gammopathy of undetermined significance cases (columns). A mean-centered gene expression is depicted by a normalized-signal pseudo-color scale as described (Eisen M, 1998). Red and green indicate over-expressed and under-expressed genes, respectively. The sample dendrogram at the top, reflecting relatedness among samples, consists of two major branches defined by over-expressed and under-expressed genes. The left branch consists of 22 monoclonal gammopathy of undetermined significance samples (horizontal blue bar) and two normal plasma cells cases (green arrows) while the right branch contains all normal plasma cells (horizontal green bar) and a subset of two monoclonal gammopathy of undetermined significance samples (blue arrows).

FIG. 2. Expression patterns of 52 genes segregate monoclonal gammopathy of undetermined significance and monoclonal gammopathy of undetermined significance-like-L multiple myeloma from non-monoclonal gammopathy of undetermined significance-like-L multiple myeloma. Two-dimensional unsupervised hierarchical cluster analysis of 52 monoclonal gammopathy of undetermined significance genes (rows) in CD138-enriched plasma cells of monoclonal gammopathy of undetermined significance (n=56), multiple myeloma evolved from monoclonal gammopathy of undetermined significance (n=16) and newly diagnosed multiple myeloma (n=351) (columns). The left branch consists of monoclonal gammopathy of undetermined significance monoclonal gammopathy of undetermined significance and monoclonal gammopathy of undetermined significance-like multiple myeloma samples (green bar) while the right branch contains the non-monoclonal gammopathy of undetermined significance-like multiple myeloma samples (red bar). The green arrows in the non-monoclonal gammopathy of undetermined significance-like multiple myeloma branch represent monoclonal gammopathy of undetermined significance cases.

FIG. 3. Expression levels of the 52 monoclonal gammopathy of undetermined significance genes in plasma cells of normal donors, and subjects with monoclonal gammopathy of undetermined significance and multiple myeloma. A color-gram is shown of the expression of the 52 genes in normal plasma cells (n=22), monoclonal gammopathy of undetermined significance and multiple myeloma from monoclonal gammopathy of undetermined significance (n=72) and multiple myeloma (n=351) (based on their location in either of the two major branches of the dendrogram in FIG. 2) and multiple myeloma cell lines (MMCL) (n=22). “monoclonal gammopathy of undetermined significance” and “multiple myeloma from monoclonal gammopathy of undetermined significance” on the left side of the figure represent those cases clustering in the monoclonal gammopathy of undetermined significance-like multiple myeloma branch of FIG. 2, while those on the right side are those clustering with the non-monoclonal gammopathy of undetermined significance-like multiple myeloma branch. Genes are indicated along the vertical axis and samples on the horizontal axis. The normalized expression value for each gene is indicated by a color, with red representing high expression and blue representing low expression. Note that normal plasma cells have a distinct pattern of over-expressed and under-expressed genes that progressively inverts with transition to monoclonal gammopathy of undetermined significance, monoclonal gammopathy of undetermined significance-like multiple myeloma, and non-monoclonal gammopathy of undetermined significance-like multiple myeloma and finally to multiple myeloma cell lines.

FIG. 4. Box plots of expression profiles of genes exhibiting common patterns. The expression levels of select genes exhibiting progressive loss (top three panels), progressive increase (middle three panels), or increased followed by decreased expression (bottom three panels) across the sample groups as ordered in FIG. 2. Sample groups are along the x-axis and the natural log transformed Affymetrix derived “signal” is plotted on the y-axis. The top, bottom and middle lines of each box correspond to the 75^(th) percentile (top quartile), 25^(th) percentile (bottom quartile) and 50^(th) percentile (median), respectively. The whiskers extend from the 10^(th) percentile (bottom decile) and top 90^(th) percentile (top decile). Open circles denote outliers within each group. The “monoclonal gammopathy of undetermined significance” and “multiple myeloma from monoclonal gammopathy of undetermined significance” on the left side of the figure represent those cases clustering in the monoclonal gammopathy of undetermined significance-like multiple myeloma branch of FIG. 2, while those on the right side are those clustering with the non-monoclonal gammopathy of undetermined significance-like multiple myeloma branch.

FIG. 5A-5B. Superior overall survival in monoclonal gammopathy of undetermined significance-like multiple myeloma and non-monoclonal gammopathy of undetermined significance-like multiple myeloma lacking amp1q21. FIG. 5A shows Kaplan-Meier estimates of overall survival in monoclonal gammopathy of undetermined significance-like multiple myeloma and non-monoclonal gammopathy of undetermined significance-like multiple myeloma demonstrated superior 5-yr actuarial probabilities of event-free survival (64% v. 44%, P=0.001) and overall survival (76% v. 59%, P=0.009) in patients with monoclonal gammopathy of undetermined significance signature. FIG. 5B shows Kaplan-Meier estimates of overall survival in monoclonal gammopathy of undetermined significance-like and non-monoclonal gammopathy of undetermined significance-like multiple myeloma according to the presence of amp1q21 by inter-phase fluorescence in situ hybridization. Amp1q21 was not a significant adverse parameter in monoclonal gammopathy of undetermined significance-like multiple myeloma but identified a high-risk group among patients with non-monoclonal gammopathy of undetermined significance-like multiple myeloma.

FIG. 6. Monoclonal gammopathy of undetermined significance-like signature is discernable in a test cohort of newly diagnosed multiple myeloma enrolled in Total Therapy 3. As in FIG. 2, a two-dimensional unsupervised hierarchical cluster analysis of 52 genes (rows) in CD138-enriched plasma cells from monoclonal gammopathy of undetermined significance (n=56), multiple myeloma evolved from monoclonal gammopathy of undetermined significance (n=16) and newly diagnosed multiple myeloma (n=213). Green arrows represent monoclonal gammopathy of undetermined significance cases clustering with so-called non-monoclonal gammopathy of undetermined significance-like multiple myeloma.

FIG. 7. Monoclonal gammopathy of undetermined significance-like signature is present in the majority of plasma cells of greater than 10 year survivors of Total Therapy 1. As in FIG. 2, a two-dimensional unsupervised hierarchical cluster analysis of 52 genes (rows) in CD138-enriched plasma cells from monoclonal gammopathy of undetermined significance (n=56), multiple myeloma from monoclonal gammopathy of undetermined significance (n=16) and newly diagnosed multiple myeloma (n=351, training cohort) and 20 long-term survivors (columns). Green arrows indicate the samples from the 20 long-term survivor.

DETAILED DESCRIPTION OF THE INVENTION

This is the first report on genomic differences recognized by global gene expression profiling using a comparative analysis between multiple myeloma and its precursor conditions monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. In an earlier report with a smaller number of cases and utilizing a first generation microarray, normal plasma cells could be distinguished from plasma cells of multiple myeloma and monoclonal gammopathy of undetermined significance combined, however the gene expression profiling was indistinguishable using plasma cells of multiple myeloma and monoclonal gammopathy of undetermined significance.

The similarity in the transcriptome between monoclonal gammopathy of undetermined significance and multiple myeloma was puzzling, as most cases of monoclonal gammopathy of undetermined significance remain clinically benign (Kyle R A, et al., 2002; Kyle R A, et al., 2006). Upon application of more sophisticated data mining approaches to a larger sample number utilizing a third generation microarray with more than 54,000 gene features, we identified differential expression of genes with roles in pathways related to cancer in normal plasma cells, and those with monoclonal gammopathy of undetermined significance and with multiple myeloma.

Although monoclonal gammopathy of undetermined significance progresses to multiple myeloma at a low annual frequency of 1%, little is known about the proportion of patients whose multiple myeloma has evolved from this precursor condition. Using unsupervised hierarchical clustering of the 52 genes differentially expressed in monoclonal gammopathy of undetermined significance and multiple myeloma, a subset of monoclonal gammopathy of undetermined significance-like multiple myeloma with favorable clinical features and longer survival was identified and further validated; the lower complete response rate may be consistent with the reestablishment of a monoclonal gammopathy of undetermined significance condition, assuming its plasma cells to be highly resistant to cytotoxic therapies (similar to normal plasma cells present at the time of bone marrow aplasia after induction therapy for acute leukemia). These results are supported by the observation of a monoclonal gammopathy of undetermined significance-like signature in the majority of patients surviving more than 10 years after initiation of Total Therapy 1 (Barlogie B, et al., 2006). Only 5% of the Total Therapy 1 long-term survivors were greater than 65 years of age at diagnosis

In addition to identifying a low-risk multiple myeloma entity with features of monoclonal gammopathy of undetermined significance, analytical clustering of monoclonal gammopathy of undetermined significance cases with non-monoclonal gammopathy of undetermined significance-like multiple myeloma may pertain to a monoclonal gammopathy of undetermined significance subset at high risk of conversion to multiple myeloma. As well subjects with multiple myeloma-like monoclonal gammopathy of undetermined significance may benefit from early therapeutic intervention in the absence of symptoms, whereas treatment may be held or deferred in patients with monoclonal gammopathy of undetermined significance-like multiple myeloma.

A “spiked” expression of MMSET (MS) and MAF/MAFB and PROLIFERATION (PR) molecular signatures together constituted high-risk disease, whereas HYPERDIPLOIDY, LOW BONE DISEASE and CCND1/CCND3 translocations represented low-risk multiple myeloma (Zhan F, et al. 2006). In this context of molecular classification of multiple myeloma, nearly 50% of monoclonal gammopathy of undetermined significance-like multiple myeloma cases and 37% of monoclonal gammopathy of undetermined significance were characterized by CCND1- or CCND3-activating translocations and CD20 expression (CD-2 designation); as opposed to only 4% of non-monoclonal gammopathy of undetermined significance-like multiple myeloma (Zhan F, et al., 2006). In contrast, the other molecular class of t(11;14)(q13;q32)-positive disease, characterized by CCND1 or CCND3 spikes and lacking CD20 expression (CD-1 designation), was significantly underrepresented in both monoclonal gammopathy of undetermined significance and monoclonal gammopathy of undetermined significance-like multiple myeloma. As expected, the molecular PROLIFERATION class was rare in monoclonal gammopathy of undetermined significance and monoclonal gammopathy of undetermined significance-like multiple myeloma (Table 1). The lower frequency of a HYPERDIPLOID molecular signature in monoclonal gammopathy of undetermined significance-like multiple myeloma relative to non-monoclonal gammopathy of undetermined significance-like multiple myeloma may suggests differences in multiple myeloma evolving or not evolving through a monoclonal gammopathy of undetermined significance state (refer to Table 1).

TABLE 1 Comparison of molecular subgroup distribution of MGUS, SMM, MM from MGUS, and newly diagnosed MM of the training set

PROLIFERATION 0 0 6 14 >.001

MMSET 2 0 13 13 >.001

CCND1-1 0 0 6 7 .001*

MAF 13 17 12 6 NS

Additionally, the infrequent presence of high-risk PROLIFERATION and MMSET genetic subtypes in monoclonal gammopathy of undetermined significance-like multiple myeloma may explain the superior survival of such patients in comparison with those exhibiting non-monoclonal gammopathy of undetermined significance-like multiple myeloma. The possibility, however, of the eventual acquisition of a non-monoclonal gammopathy of undetermined significance-like and PROLIFERATION signature with progression has to be considered. The presence of a CD-2 signature, originally recognized in multiple myeloma, in many cases of monoclonal gammopathy of undetermined significance and monoclonal gammopathy of undetermined significance-like multiple myeloma, will be helpful in ascertaining whether other multiple myeloma subtypes may have evolved from a monoclonal gammopathy of undetermined significance phase. Conversely, we can investigate whether a shift occurs to a non-monoclonal gammopathy of undetermined significance-like signature with progression. Longitudinal studies on a case-by-case basis will reveal insight into the molecular changes accompanying progression in an individual patient.

Due to technical limitations, it is not clear whether the gene expression profiling differences between monoclonal gammopathy of undetermined significance, monoclonal gammopathy of undetermined significance-like multiple myeloma and non-monoclonal gammopathy of undetermined significance-like multiple myeloma are due to a dilution effect caused by co-purification of normal plasma cells or heterogeneity among clonally related tumor cells. Support for the latter possibility comes from the observation that TNFSF7/CD27, one of the genes in the current list of 52, is progressively down regulated in the transition from normal plasma cells to monoclonal gammopathy of undetermined significance to multiple myeloma (Guikema J E, et al., 2003). Using flow cytometry, Moreau et al. noted CD27 expression in plasma cells of all normal donors, its absence in 36% of patients with multiple myeloma at diagnosis and in 47% at relapse, as well as in 92% of human glomerular mesangial cell line (HMCL); survival was superior in CD27-positive versus CD27-negative multiple myeloma (Moreau P, et al., 2006). The agreement between the gene expression profiling data here and previously published protein expression studies supports our contention that the observed differences in plasma cells of normal donors and patients with monoclonal gammopathy of undetermined significance and patients with multiple myeloma are specific to the disease process rather than due to contamination by normal plasma cells.

A high-resolution map of recurrent, minimal common regions of gain/amplification and loss/deletion was recently reported along with the genes residing in these minimal common regions, whose expression was strongly correlated with changes in copy number. Over-expression of genes in multiple myeloma relative to monoclonal gammopathy of undetermined significance pertained to CCT3 and HIST2H2AA mapping to minimal common regions at 1q21-1q22. It was recently shown that fluorescent in situ hybridization-defined amplification of 1q21 was absent in monoclonal gammopathy of undetermined significance; its presence in some patients with smoldering multiple myeloma was associated with a higher risk of conversion to multiple myeloma, and its presence in multiple myeloma conferred short survival (Hanamura I, et al., 2006). Other genes included SLC39A8 mapping to 4q22.3-4q24 and ASK/DBF4 mapping to 7q21.12. Genes mapping to minimal common regions with loss/deletion and reduced expression in multiple myeloma relative to monoclonal gammopathy of undetermined significance included the Caspase Recruitment Domain-Containing Protein 15 (CARD15) mapping at 16q11.2 and the fork-head box O1A (FOXO1A) transcription factor mapping near the peak of a minimal common region at 13q14.1. The identification of genes, whose expression level is copy number-sensitive in multiple myeloma, as being differentially expressed in a comparison of monoclonal gammopathy of undetermined significance and multiple myeloma, again suggests that differences are not likely to simply reflect the degree of contamination of normal plasma cells in the CD138-selected fractions and that the altered expression of this small subset of genes is important in disease progression.

In conclusion, genomic profiling was used to identify a subset of genes whose expression patterns differentiate plasma cells from normal donors and subjects with monoclonal gammopathy of undetermined significance and multiple myeloma. Patients with monoclonal gammopathy of undetermined significance, exhibiting molecular features of multiple myeloma and deemed at higher risk of conversion to overt multiple myeloma, could be selected for secondary prevention trials. The prevalence of a monoclonal gammopathy of undetermined significance-like signature in plasma cells of long-term survivors of Total Therapy 1 raises the question whether these superior results could have been achieved with less aggressive treatment strategies. Investigation of the functional pathways of genes with differential expression levels in the various plasma cell dyscrasias may provide valuable insights into the enigmatic mechanisms of the multi-step molecular pathogenesis of multiple myeloma.

In one embodiment of the present invention there is a method of gene expression profiling for the identification of genomic signatures specific for a disease by performing a comparative analysis on data obtained from hybridization of nucleic acid isolated from an individual, to a DNA microarray. Specifically, the genomic signature may be defined by a gene(s) that is differentially expressed in plasma cells from the precursor form(s) of the disease in comparison to the expression of the gene in plasma cell of normal and/or plasma cell of the disease. Preferably, the disease is multiple myeloma and its precursor state is monoclonal gammopathy of undetermined significance or smoldering multiple myeloma. In general, the genes may be selected from a group of 52 consisting of ABCC10, ASK, ATP11B, ATP13A3, AVEN, BCL11A, C11orf1, C12orf11, C15orf24, C1QBP, C9orf41, CARD15, CCT3, DKC1, FOXO1A, GPI, HIST1H1C, HIST1H2AC, HIST2H2AA, HIST2H2BE, HSPA9B, IPO7, KIAA0179, KIAA049, KLF2, LARS, LOC15909, LOC550643, MED28, MRPL32, MYO6, NBEA, NIFIE14, NME1, OTUD6B, PAIC, PDE4B, RANBP2L1, RCN2, RIPK3, RPL37A, SLC39A8, SMAD5, SSBP1, TCERG, TMEM57, TNFRSF7, TXN, UXS1, VDAC1, ZA20D2, and ZNF131.

In another embodiment of the present invention genes involved in various cellular processes comprised of cell cycle control, DNA synthesis, chromosome assembly, nuclear protein import, gene transcription, cell aging, cell signaling, metabolism, energy production, ion transport, reactive oxygen metabolism, drug resistance or programmed cell death/apoptosis, are significantly differentially expressed in normal plasma cells and plasma cells of monoclonal gammopathy of undetermined significance and/or multiple myeloma (Tables 2 and 3).

TABLE 2 Genes Significantly Differentially Expressed between normal plasma cells and plasma cells of monoclonal gammopathy of undetermined significance Probe Set Symbol Map Location SAM SCORE 1555852_at — 06 6.56 224820_at FAM36A 1q44 6.20 205383_s_at ZBTB20 3q13.2 6.18 221875_x_at HLA-F 6p21.3 5.92 213158_at — 03 5.65 227527_at MLL2 12q12-q14 5.41 209398_at HIST1H1C 6p21.3 5.39 232304_at PELI1 2p13.3 5.36 213720_s_at SMARCA4 19p13.2 5.27 217436_x_at HLA-G /// HLA-H 6p21.3 5.26 202081_at IER2 19p13.13 5.21 228465_at — 01 5.19 232431_at NR3C1 5q31 5.11 225256_at — 19 5.08 201531_at ZFP36 19q13.1 5.05 216321_s_at NR3C1 5q31.3 5.00 212137_at LARP1 5q33.2 4.99 228053_s_at C9orf105 9p13.1 4.97 230003_at — 12 4.90 201074_at SMARCC1 3p23-p21 4.85 227749_at — 19 4.84 225917_at — 12 4.82 1553704_x_at FLJ90396 19p13.2-p13.13 4.81 212130_x_at SUI1 17q21.2 4.79 225547_at — 08 4.78 214143_x_at RPL24 /// SLC36A2 3q12 /// 5q33.1 4.76 201788_at DDX42 17q23.3 4.75 204806_x_at HLA-F 6p21.3 4.73 200840_at KARS 16q23-q24 4.71 201263_at TARS 5p13.2 4.70 210110_x_at HNRPH3 10q22 4.67 203080_s_at BAZ2B 2q23-q24 4.66 200830_at PSMD2 3q27.1 4.61 208956_x_at DUT 15q15-q21.1 4.60 226981_at MLL 11q23 4.60 214317_x_at RPS9 19q13.4 4.60 202284_s_at CDKN1A 6p21.2 4.58 214356_s_at KIAA0368 9q31.3 4.56 225431_x_at ACY1L2 6q15 4.55 1558956_s_at WDR56 3q25.33 4.54 1553703_at FLJ90396 19p13.2-p13.13 4.53 225390_s_at KLF13 15q12 4.53 212665_at TIPARP 3q25.31 4.48 200085_s_at TCEB2 16p12.3 4.48 218797_s_at SIRT7 17q25 4.48 200072_s_at HNRPM 19p13.3-p13.2 4.46 224610_at RNU22 11q13 4.45 224579_at SLC38A1 12q13.11 4.44 235308_at ZBTB20 3q13.2 4.43 225190_x_at RPL35A 3q29-qter 4.43 200019_s_at FAU 11q13 4.42 218319_at PELI1 2p13.3 4.42 201498_at USP7 16p13.3 4.41 227121_at — 03 4.41 202946_s_at BTBD3 20p12.2 4.40 202649_x_at RPS19 19q13.2 4.40 209806_at HIST1H2BK 6p21.33 4.40 219762_s_at RPL36 19p13.3 4.39 225097_at HIPK2 7q32-q34 4.38 201405_s_at COPS6 7q22.1 4.38 227878_s_at SPATA11 19p13.3 4.38 203038_at PTPRK 6q22.2-23.1 4.37 203538_at CAMLG 5q23 4.35 228690_s_at NDUFA11 19p13.3 4.34 218263_s_at LOC58486 11p15.3 4.34 224604_at LOC401152 4q26 4.33 213801_x_at RPSA /// LOC388524 /// 3p22.2 /// 19p12 /// 1p21.1 4.31 LOC388654 221791_s_at HSPC016 3p21.31 4.31 218557_at NIT2 3q12.2 4.30 201226_at NDUFB8 10q23.2-q23.33 4.28 201119_s_at COX8A 11q12-q13 4.28 212971_at CARS 11p15.5 4.27 204918_s_at MLLT3 9p22 4.27 226620_x_at DAZAP1 19p13.3 4.27 213857_s_at CD47 3q13.1-q13.2 4.27 220966_x_at ARPC5L 9q33.3 4.26 219863_at HERC5 4q22.1-q23 4.26 218286_s_at RNF7 3q22-q24 4.25 218280_x_at HIST2H2AA 1q21.2 4.24 203525_s_at APC 5q21-q22 4.23 202309_at MTHFD1 14q24 4.23 222735_at TMEM38B 9q31.2 4.22 225814_at XRN1 3q23 4.22 211698_at CRI1 15q21.1-q21.2 4.21 201258_at RPS16 19q13.1 4.18 212428_at KIAA0368 9q31.3 4.18 224702_at MGC23909 5q14.2 4.18 203190_at NDUFS8 11q13 4.18 201892_s_at IMPDH2 3p21.2 4.18 211799_x_at HLA-C 6p21.3 4.18 205659_at HDAC9 7p21.1 4.18 205569_at LAMP3 3q26.3-q27 4.17 226225_at MCC 5q21-q22 4.17 214988_s_at SON 21q22.1-q22.2|21q22.11 4.15 212450_at KIAA0256 15q21.1 4.14 212826_s_at SLC25A6 Xp22.32 and Yp 4.12 200843_s_at EPRS 1q41-q42 4.11 212276_at LPIN1 2p25.1 4.11 212959_s_at MGC4170 12q23.3 4.09 224439_x_at RNF7 3q22-q24 4.09 200899_s_at MGEA5 10q24.1-q24.3 4.08 201030_x_at LDHB 12p12.2-p12.1 4.08 202243_s_at PSMB4 1q21 4.07 211730_s_at POLR2L 11p15 4.07 202839_s_at NDUFB7 19p13.12-p13.11 4.07 202818_s_at TCEB3 1p36.1 4.06 202779_s_at UBE2S 19q13.43 4.06 200691_s_at HSPA9B 5q31.1 4.05 225434_at DEDD2 19q13.2 4.05 218205_s_at MKNK2 19p13.3 4.05 224741_x_at GAS5 1q23.3 4.05 209685_s_at PRKCB1 16p11.2 4.05 200089_s_at RPL4 15q22 4.04 224719_s_at GRCC10 12p13.31 4.04 200632_s_at NDRG1 8q24.3 4.04 201306_s_at ANP32B 9q22.32 4.03 201086_x_at SON 21q22.1-q22.2|21q22.11 4.03 213041_s_at ATP5D 19p13.3 4.03 203113_s_at EEF1D 8q24.3 4.02 200786_at PSMB7 9q34.11-q34.12 4.01 221290_s_at MUM1 19p13.3 4.01 203725_at GADD45A 1p31.2-p31.1 4.00 209058_at EDF1 9q34.3 3.99 225321_s_at PILRB 7q22.1 3.99 217853_at TENS1 7p13-p12.3 3.99 226370_at KLHL15 Xp22.1-p21 3.99 226873_at — 15 3.99 203449_s_at TERF1 8q13 3.99 214290_s_at HIST2H2AA 1q21.2 3.98 202244_at PSMB4 1q21 3.98 222389_s_at WAC 10 3.98 213510_x_at LOC220594 17p11.2 3.96 212254_s_at DST 6p12-p11 3.96 200631_s_at SET 9q34 3.95 226252_at — 03 3.94 232889_at LOC153561 5q13.2 3.94 228702_at FLJ43663 7q32.3 3.94 226385_s_at C7orf30 7p15.3 3.94 226447_at ASH1L 1q22 3.93 200055_at TAF10 11p15.3 3.93 217810_x_at LARS 5q32 3.92 202110_at COX7B Xq21.1 3.91 217828_at FLJ13213 15q21.3 3.91 211752_s_at NDUFS7 19p13.3 3.91 204093_at CCNH 5q13.3-q14 3.90 201952_at ALCAM 3q13.1 3.90 204254_s_at VDR 12q13.11 3.90 218306_s_at HERC1 15q22 3.90 203529_at PPP6C 9q33.3 3.90 226465_s_at SON 21q22.1-q22.2|21q22.11 3.89 228046_at LOC152485 4q31.21-q31.22 3.89 213309_at PLCL2 3p24.3 3.88 212048_s_at YARS 1p35.1 3.88 200807_s_at HSPD1 2q33.1 3.87 200002_at RPL35 9q34.1 3.87 225421_at ACY1L2 6q15 3.87 215696_s_at KIAA0310 9q34.3 3.86 218882_s_at WDR3 1p13-p12 3.85 226720_at KIAA1935 5q33.3 3.85 202396_at TCERG1 5q31 3.85 213025_at THUMPD1 16p12.3 3.84 211623_s_at FBL 19q13.1 3.83 225028_at LOC550643 Xp11.1 3.83 201164_s_at PUM1 1p35.2 3.83 203752_s_at JUND 19p13.2 3.82 225429_at PPP6C 9q33.3 3.81 202682_s_at USP4 3p21.3 3.81 219371_s_at KLF2 19p13.13-p13.11 3.81 202657_s_at SERTAD2 2p14 3.80 212066_s_at USP34 2p15 3.79 218533_s_at UCKL1 20q13.33 3.79 40189_at SET 9q34 3.78 201967_at RBM6 3p21.3 3.78 225956_at LOC153222 5q35.1 3.78 226505_x_at USP32 17q23.2 3.78 200999_s_at CKAP4 12q23.3 3.78 211075_s_at CD47 3q13.1-q13.2 3.77 225153_at GFM1 3q25.1-q26.2 3.77 223193_x_at E2IG5 3q21.1 3.77 225951_s_at — 15q26.1 3.76 212716_s_at EIF3S12 19q13.2 3.76 39729_at PRDX2 19p13.2 3.76 241775_at SCFD1 14q12 3.75 212733_at KIAA0226 3q29 3.73 222427_s_at LARS 5q32 3.73 213414_s_at RPS19 19q13.2 3.73 200014_s_at HNRPC 14q11.2 3.72 226116_at — 01 3.72 206158_s_at ZNF9 3q21 3.72 217491_x_at COX7C 5q14 3.72 226915_s_at ARPC5L 9q33.3 3.71 221847_at LOC440123 12p13.33 3.70 225477_s_at MRPS25 3p25 3.70 1555945_s_at C9orf10 9q22.31 3.69 239893_at MCTP2 15q26.2 3.69 217726_at COPZ1 12q13.2-q13.3 3.69 213737_x_at LOC283768 /// LOC388080 /// 15q13.1 /// 15q11.2 /// 3.69 LOC388189 /// LOC390535 /// 15p13 LOC400304 /// LOC440234 /// DKFZp434P162 208729_x_at HLA-B 6p21.3 3.69 208873_s_at C5orf18 5q22-q23 3.68 221267_s_at C19orf27 19p13.3 3.68 222200_s_at BSDC1 1p35.1 3.68 202021_x_at SUI1 17q21.2 3.67 226109_at C21orf91 21q21.1 3.67 225698_at TIGA1 5q21-q22 3.66 200995_at IPO7 11p15.4 3.66 1553979_at — 3.66 208623_s_at VIL2 6q25.2-q26 3.66 208691_at TFRC 3q29 3.66 222589_at NLK 17q11.2 3.66 212205_at H2AFV 7p13 3.65 235381_at HBXAP 11q13.5 3.65 200094_s_at EEF2 19pter-q12 3.64 222992_s_at NDUFB9 8q13.3 3.64 207769_s_at PQBP1 Xp11.23 3.64 203880_at COX17 3q13.33 3.64 222428_s_at LARS 5q32 3.64 212132_at FAM61A 19q13.11 3.63 224841_x_at GAS5 1q23.3 3.63 212640_at PTPLB 3q21.1 3.63 217707_x_at SMARCA2 9p22.3 3.62 207996_s_at C18orf1 18p11.2 3.62 203832_at SNRPF 12q23.1 3.62 200022_at RPL18 19q13 3.62 214280_x_at HNRPA1 12q13.1 3.62 226453_at AYP1 11q13.1 3.61 223008_s_at C9orf5 9q31 3.61 218239_s_at GTPBP4 10p15-p14 3.59 223003_at MGC2803 19p13.13 3.59 208101_s_at C9orf74 9q34.11 3.59 218149_s_at ZNF395 8p21.1 3.59 213864_s_at NAP1L1 12q21.2 3.59 203133_at SEC61B 9q22.32-q31.3 3.58 203556_at ZHX2 8q24.13 3.58 221692_s_at MRPL34 19p13.1 3.58 225517_at FLJ20582 15q14 3.58 206055_s_at SNRPA1 15q26.3 3.58 201577_at NME1 17q21.3 3.57 228341_at FLJ31265 3q21.3 3.57 226340_x_at LOC349338 /// FLJ25222 /// Xq28; Yq12 /// 15q26.3 /// 3.57 MGC52000 2q14.1 212301_at RTF1 15q15.1 3.57 202090_s_at UQCR 19p13.3 3.56 214351_x_at RPL13 /// LOC388344 16q24.3|17p11.2 /// 3.55 17p11.2 207957_s_at PRKCB1 16p11.2 3.55 214687_x_at ALDOA 16q22-q24 3.55 226352_at JMY 5q14.1 3.55 225229_at AFF4 5q31 3.55 215359_x_at ZNF44 19p13.2 3.54 208988_at FBXL11 11q13.2 3.54 223480_s_at MRPL47 3q26.33 3.54 200774_at C9orf10 9q22.31 3.54 201153_s_at MBNL1 3q25 3.54 221475_s_at RPL15 3p24.2 3.53 209059_s_at EDF1 9q34.3 3.53 200013_at RPL24 3q12 3.53 217936_at ARHGAP5 14q12 3.53 201611_s_at ICMT 1p36.21 3.53 201460_at MAPKAPK2 1q32 3.52 224722_at MIB1 18q11.2 3.51 213891_s_at TCF4 18q21.1 3.51 200797_s_at MCL1 1q21 3.51 230261_at ST8SIA4 5q21 3.51 202314_at CYP51A1 7q21.2-q21.3 3.51 228988_at ZNF6 Xq21.1-q21.2 3.50 210942_s_at ST3GAL6 3q12.1 3.50 201676_x_at PSMA1 11p15.1 3.50 208827_at PSMB6 17p13 3.50 225610_at UHRF2 9p24.1 3.50 1552519_at ACVR1C 2q24.1 3.50 210347_s_at BCL11A 2p16.1 3.48 207573_x_at ATP5L 11q23.3 3.48 228345_at CHIC1 Xq13-q21 3.48 226191_at GSK3B 3q13.3 3.48 204917_s_at MLLT3 9p22 3.48 229813_x_at DAZAP1 19p13.3 3.48 226052_at BRD4 19p13.1 3.47 215071_s_at HIST1H2AC 6p21.3 3.47 213331_s_at NEK1 4q33 3.47 1555837_s_at POLR2B 4q12 3.47 226939_at CPEB2 4p15.33 3.47 226941_at ATF6 1q22-q23 3.46 204571_x_at PIN4 Xq13 3.46 204020_at PURA 5q31 3.46 213726_x_at TUBB2 9q34 3.46 207761_s_at DKFZP586A0522 12q13.12 3.45 200770_s_at LAMC1 1q31 3.45 211800_s_at USP4 3p21.3 3.45 208634_s_at MACF1 1p32-p31 3.45 217969_at C11orf2 11q13 3.45 218194_at DKFZP566E144 11q23.1-q23.2 3.45 235005_at MGC4562 15q22.31 3.45 209911_x_at HIST1H2BD 6p21.3 3.45 202646_s_at CSDE1 1p22 3.45 213360_s_at POM121 /// LOC340318 /// 7q11.23 3.45 LOC441253 218381_s_at U2AF2 19q13.42 3.44 200823_x_at RPL29 3p21.3-p21.2 3.44 214394_x_at — 06 3.44 221773_at ELK3 12q23 3.44 211946_s_at BAT2D1 1q23.3 3.43 211784_s_at SFRS1 17q21.3-q22 3.43 225361_x_at LOC159090 Xq26.3 3.43 230836_at ST8SIA4 5q21 3.43 214800_x_at BTF3 /// LOC345829 5q13.2 /// 6q25.1 3.43 238761_at MED28 4p16 3.43 232213_at PELI1 2p13.3 3.43 209903_s_at ATR 3q22-q24 3.43 210346_s_at CLK4 5q35 3.43 221207_s_at NBEA 13q13 3.42 212227_x_at SUI1 17q21.2 3.42 229353_s_at NUCKS1 1q32.1 3.42 209267_s_at SLC39A8 4q22-q24 3.41 211671_s_at NR3C1 5q31.3 3.41 214894_x_at MACF1 1p32-p31 3.41 226312_at AVO3 5p13.1 3.41 208113_x_at PABPC3 13q12-q13 3.41 1555844_s_at HNRPM 19p13.3-p13.2 3.40 200715_x_at RPL13A 19q13.3 3.39 222978_at SURF4 9q34.2 3.39 200772_x_at PTMA 2q35-q36 3.39 208692_at RPS3 11q13.3-q13.5 3.39 1557820_at AFG3L2 18p11 3.39 226283_at WDR51B 12q21.33 3.38 211746_x_at PSMA1 11p15.1 3.38 208659_at CLIC1 6p22.1-p21.2 3.38 228956_at UGT8 4q26 3.38 218265_at SECISBP2 9q22.2 3.38 202941_at NDUFV2 18p11.31-p11.2 3.37 227370_at KIAA1946 2q32.1 3.37 209503_s_at PSMC5 17q23-q25 3.37 211911_x_at HLA-B 6p21.3 3.37 209329_x_at MGC2198 5q35.2 3.36 209143_s_at CLNS1A /// C3orf4 11q13.5-q14 /// 3p11-q11 3.36 202983_at SMARCA3 3q25.1-q26.1 3.36 213077_at YTHDC2 5q22.2 3.36 222415_at MLL3 7q34-q36 3.36 201397_at PHGDH 1p12 3.36 202824_s_at TCEB1 8q21.11 3.36 200877_at CCT4 2p15 3.35 203688_at PKD2 4q21-q23 3.35 200000_s_at PRPF8 17p13.3 3.35 226344_at ZMAT1 Xq21 3.35 201134_x_at COX7C 5q14 3.34 212967_x_at NAP1L1 12q21.2 3.34 214853_s_at SHC1 1q21 3.34 201031_s_at HNRPH1 5q35.3 3.34 208771_s_at LTA4H 12q22 3.33 36553_at ASMTL Xp22.3; Yp11.3 3.33 226808_at KIAA0543 7q36.1 3.33 211036_x_at ANAPC5 12q24.31 3.33 218134_s_at RBM22 5q33.1 3.33 211445_x_at FKSG17 /// LOC389240 8q22.3 /// 4q32.3 3.33 201865_x_at NR3C1 5q31.3 3.32 205644_s_at SNRPG 2p13.3 3.32 213588_x_at RPL14 3p22-p21.2 3.32 200990_at TRIM28 19q13.4 3.31 213893_x_at PMS2L5 7q11-q22 3.31 201678_s_at DC12 3q21.3 3.31 1558142_at TNRC6B 22q13.1 3.31 210453_x_at ATP5L 11q23.3 3.30 208746_x_at ATP5L 11q23.3 3.30 226496_at ZCCHC7 9p13.2 3.30 217798_at CNOT2 12q15 3.30 223245_at STRBP 9q33.3 3.29 225368_at HIPK2 7q32-q34 3.29 218236_s_at PRKD3 2p21 3.29 213846_at COX7C 5q14 3.29 238436_s_at LOC390980 19q13.43 3.29 201473_at JUNB 19p13.2 3.28 200662_s_at TOMM20 1q42 3.28 204172_at CPOX 3q12 3.28 208916_at SLC1A5 19q13.3 3.28 201754_at COX6C 8q22-q23 3.27 203753_at TCF4 18q21.1 3.27 221700_s_at UBA52 19p13.1-p12 3.27 229394_s_at GRLF1 19q13.3 3.27 201876_at PON2 7q21.3 3.26 218772_x_at TMEM38B 9q31.2 3.26 204244_s_at ASK 7q21.3 3.25 223101_s_at ARPC5L 9q33.3 3.25 209606_at PSCDBP 2q11.2 3.25 223705_s_at GPBP1 5q11.2 3.25 202265_at PCGF4 10p11.23 3.24 224679_at MESDC2 15q13 3.24 242691_at — 19 3.24 201637_s_at FXR1 3q28 3.24 222669_s_at SBDS 7q11.21 3.24 218281_at MRPL48 11q13.4 3.24 227189_at CPNE5 6p21.1 3.24 225093_at UTRN 6q24 3.23 205934_at PLCL1 2q33 3.23 211921_x_at PTMA 2q35-q36 3.23 212773_s_at TOMM20 1q42 3.23 221829_s_at TNPO1 5q13.2 3.23 201803_at POLR2B 4q12 3.23 225065_x_at MGC40157 17p11.2 3.23 215016_x_at DST 6p12-p11 3.23 212155_at RNF187 1q42.13 3.23 209703_x_at DKFZP586A0522 12q13.12 3.22 210231_x_at SET 9q34 3.22 225526_at MKLN1 7q32 3.22 218200_s_at NDUFB2 7q34 3.22 226449_at FLJ36090 5q23.2 3.22 200810_s_at CIRBP 19p13.3 3.22 226392_at — 03 3.22 201517_at NCBP2 3q29 3.22 225973_at TAP2 6p21.3 3.21 226626_at THOC2 Xq25-q26.3 3.21 229686_at P2RY8 Xp22.33; Yp11.3 3.21 229742_at LOC145853 15q23 3.21 203366_at POLG 15q25 3.21 202737_s_at LSM4 19p13.11 3.21 211969_at HSPCA 14q32.33 3.20 217747_s_at RPS9 19q13.4 3.20 226914_at ARPC5L 9q33.3 3.20 213005_s_at ANKRD15 9p24.3 3.20 217773_s_at NDUFA4 7p21.3 3.20 218459_at TOR3A 1q25.2 3.20 201281_at ADRM1 20q13.33 3.20 208713_at HNRPUL1 19q13.2 3.19 222673_x_at TMEM57 /// LOC159090 1p36.11 /// Xq26.3 3.19 222891_s_at BCL11A 2p16.1 3.19 208887_at EIF3S4 19p13.2 3.19 225290_at — 12 3.19 202887_s_at DDIT4 10pter-q26.12 3.19 204976_s_at AMMECR1 Xq22.3 3.18 211961_s_at RAB7 3q21.3 3.18 203189_s_at NDUFS8 11q13 3.18 213564_x_at LDHB 12p12.2-p12.1 3.18 227284_at LOC90321 19q13.41 3.18 209654_at KIAA0947 5p15.32 3.18 212247_at NUP205 7q33 3.17 221434_s_at C14orf156 14q24.3 3.17 212018_s_at RSL1D1 16p13.13 3.17 229460_at — 02 3.17 201268_at NME2 17q21.3 3.17 223084_s_at CCNDBP1 15q14-q15 3.17 225304_s_at NDUFA11 19p13.3 3.17 210776_x_at TCF3 19p13.3 3.17 213485_s_at ABCC10 6p21.1 3.17 204461_x_at RAD1 5p13.2 3.17 224345_x_at E2IG5 3q21.1 3.16 228961_at — 05 3.16 54632_at THADA 2p21 3.16 217768_at C14orf166 14q22.1 3.16 205690_s_at G10 7q22.1 3.16 227538_at CRSP7 19p13.11 3.16 204559_s_at LSM7 19p13.3 3.16 209974_s_at BUB3 10q26 3.15 200050_at ZNF146 19q13.1 3.15 209579_s_at MBD4 3q21-q22 3.14 224511_s_at TXNL5 17p13.1 3.14 224624_at LRRC8A 9q34.11 3.14 217980_s_at MRPL16 11 3.14 201038_s_at ANP32A 15q22.3-q23 3.13 209323_at PRKRIR 11q13.5 3.13 216570_x_at RPL29 /// LOC283412 /// 3p21.3-p21.2 /// 12q22 /// 3.13 LOC284064 /// LOC389655 /// 17q21.31 /// 8q11.21 /// LOC391738 /// LOC401911 5p15.2 /// 19q13.11 209302_at POLR2H 3q28 3.13 224932_at C22orf16 22q11.23 3.13 208647_at FDFT1 8p23.1-p22 3.13 225155_at C6orf160 6q14.3 3.13 215823_x_at PABPC3 /// PABPC1 /// 13q12-q13 /// 8q22.2-q23 3.13 LOC341315 /// 12q14.2 225223_at SMAD5 5q31 3.12 200874_s_at NOL5A 20p13 3.12 207760_s_at NCOR2 12q24 3.12 202956_at ARFGEF1 8q13 3.12 201587_s_at IRAK1 Xq28 3.11 212248_at LYRIC 8q22.1 3.11 225144_at BMPR2 2q33-q34 3.11 211928_at DNCH1 14q32.3-qter|14q32 3.11 212501_at CEBPB 20q13.1 3.11 218570_at KBTBD4 11p11.2 3.11 202329_at CSK 15q23-q25 3.11 218320_s_at NDUFB11 Xp11.3 3.11 211710_x_at RPL4 15q22 3.10 202419_at FVT1 18q21.3 3.10 221494_x_at EIF3S12 19q13.2 3.10 200816_s_at PAFAH1B1 17p13.3 3.10 224961_at SCYL2 12q23.1 3.10 224664_at C10orf104 10q22.1 3.10 201221_s_at SNRP70 19q13.3 3.09 226098_at WDR56 3q25.33 3.09 201726_at ELAVL1 19p13.2 3.09 206542_s_at SMARCA2 9p22.3 3.09 211933_s_at HNRPA3 2q31.2 3.09 225764_at ETV6 12p13 3.09 221891_x_at HSPA8 11q24.1 3.08 225415_at DTX3L 3q21.1 3.08 219497_s_at BCL11A 2p16.1 3.08 207551_s_at MSL3L1 Xp22.3 3.08 235035_at SLC35E1 19p13.11 3.08 203621_at NDUFB5 3q26.33 3.08 212842_x_at RANBP2L1 /// DKFZp686P0288 2q13 /// 2q12.3 3.07 /// LOC375258 213251_at — 4q31.21 3.07 219097_x_at MGC2747 19p13.11 3.07 200818_at ATP5O 21q22.1-q22.2|21q22.11 3.07 225179_at HIP2 4p14 3.07 213166_x_at FLJ14346 2q21.1 3.06 200063_s_at NPM1 5q35 3.06 218053_at FNBP3 2q23.3 3.06 235879_at MBNL1 3q25 3.06 235360_at — 02 3.05 213186_at DZIP3 3q13.13 3.05 200873_s_at CCT8 21q22.11 3.05 200959_at FUS 16p11.2 3.05 208693_s_at GARS 7p15 3.05 200097_s_at HNRPK 9q21.32-q21.33 3.04 210891_s_at GTF2I /// GTF2IP1 7q11.23 3.04 235372_at FCRLM1 1q23.3 3.04 223134_at BBX 3q13.1 3.04 201812_s_at TOMM7 /// LOC201725 7p15.3 /// 4q32.1 3.03 200017_at RPS27A 2p16 3.03 222465_at C15orf15 /// LOC284288 15q21 /// 18q21.31 3.03 239258_at PIGF 2p21-p16 3.03 209932_s_at DUT 15q15-q21.1 3.03 212058_at SR140 3q23 3.03 237475_x_at — 05 3.03 223034_s_at C1orf43 1q21.2 3.03 220755_s_at C6orf48 6p21.3 3.03 227624_at KIAA1546 4q24 3.03 226789_at — 01 3.02 45828_at FLJ10241 19q13.2 3.02 212689_s_at JMJD1A 2p11.2 3.02 205771_s_at AKAP7 6q23 3.02 200629_at WARS 14q32.31 3.02 218334_at NIF3L1BP1 3p14.1 3.01 212467_at DNAJC13 3q22.1 3.01 203818_s_at SF3A3 1p34.3 3.01 207320_x_at STAU 20q13.1 3.01 217759_at TRIM44 11p13 3.01 223042_s_at FUNDC2 Xq28 3.01 226662_at STX17 9q31.1 3.01 203227_s_at SAS 12q13.3 3.01 217926_at HSPC023 19p13.13 3.01 203685_at BCL2 18q21.33|18q21.3 3.00 208986_at TCF12 15q21 3.00 233929_x_at FLJ25222 15q26.3 3.00 226110_at PTAR1 9q21.11 3.00 222997_s_at MRPS21 01 3.00 212566_at MAP4 3p21 3.00 201154_x_at RPL4 15q22 2.99 223061_at MGC3234 11p15.5 2.99 228574_at DKFZp762A217 12q21.31 2.99 208697_s_at EIF3S6 8q22-q23 2.99 222414_at MLL3 7q34-q36 2.99 227186_s_at MRPL41 9q34.3 2.99 226077_at FLJ31951 5q33.3 2.98 211931_s_at HNRPA3 2q31.2 2.98 212840_at KIAA0794 3q29 2.97 226684_at C14orf103 14q32.2 2.97 217733_s_at TMSB10 2p11.2 2.97 213762_x_at RBMX Xq26.3 2.97 200834_s_at RPS21 20q13.3 2.97 201186_at LRPAP1 4p16.3 2.96 220864_s_at NDUFA13 19p13.2 2.96 200093_s_at HINT1 5q31.2 2.96 224599_at CGGBP1 3p12-p11.1 2.96 200023_s_at EIF3S5 11p15.4 2.96 224581_s_at NUCKS 1q32.1 2.96 213128_s_at UBE3A 15q11-q13 2.96 224565_at TncRNA 11q13.1 2.96 214271_x_at RPL12 9q34 2.96 228332_s_at C11orf31 11q12.1 2.95 203252_at CDK2AP2 11q13 2.95 229861_at LOC440426 17q12 2.95 203396_at PSMA4 15q25.1 2.95 212690_at DDHD2 8p12 2.95 209036_s_at MDH2 7p12.3-q11.2 2.95 212927_at SMC5L1 9q21.11 2.94 204516_at ATXN7 3p21.1-p12 2.94 208709_s_at NRD1 1p32.2-p32.1 2.94 213356_x_at HNRPA1 /// LOC284387 /// 12q13.1 /// 19p13.2 /// 2.94 LOC285984 /// LOC344741 /// 7q21.11 /// 3q24 /// LOC388275 /// LOC389674 /// 16q12.1 /// 8q21.13 /// LOC391670 /// LOC402112 /// 4q21.21 /// 2q31.1 /// LOC402562 /// LOC439963 /// 10q11.22 /// 13q12.11 /// LOC440125 /// LOC441507 Xq22.1 208799_at PSMB5 14q11.2 2.94 212987_at FBXO9 6p12.3-p11.2 2.94 201393_s_at IGF2R 6q26 2.93 221518_s_at USP47 11p15.3 2.93 203301_s_at DMTF1 7q21 2.93 41220_at 9-Sep 17q25 2.93 210976_s_at PFKM 12q13.3 2.93 201216_at C12orf8 12q24.13 2.92 202277_at SPTLC1 9q22.2 2.92 203026_at ZBTB5 9p13.2 2.92 208021_s_at RFC1 4p14-p13 2.92 223176_at C6orf69 6p21.31 2.92 203531_at CUL5 11q22-q23 2.91 1564637_s_at FLJ38426 15q14 2.91 224644_at — 03 2.91 225892_at IREB2 15q25.1 2.91 202264_s_at TOMM40 19q13 2.91 205239_at AREG 4q13-q21 2.91 226006_at — 03 2.91 212426_s_at YWHAQ 2p25.1 2.91 203825_at BRD3 9q34 2.91 221190_s_at C18orf8 18q11.2 2.90 208864_s_at TXN 9q31 2.90 221570_s_at METTL5 2q31.1 2.90 38269_at PRKD2 19q13.3 2.90 202491_s_at IKBKAP 9q31 2.90 208706_s_at EIF5 14q32.32 2.89 205633_s_at ALAS1 3p21.1 2.89 226386_at C7orf30 7p15.3 2.89 225561_at SELT 3q25.1 2.89 211971_s_at LRPPRC 2p21 2.89 231995_at C9orf82 9p21.2 2.88 204068_at STK3 8q22.2 2.88 201746_at TP53 17p13.1 2.88 225912_at TP53INP1 8q22 2.88 209898_x_at ITSN2 2pter-p25.1 2.88 213860_x_at CSNK1A1 5q32 2.87 234512_x_at LOC442159 6p24.3 2.87 227636_at THAP5 7q31.1 2.87 209337_at PSIP1 9p22.3 2.87 226635_at — 9p13.2 2.87 201305_x_at ANP32B 9q22.32 2.87 222996_s_at CXXC5 5q31.2 2.87 223238_s_at — 13 2.87 225219_at SMAD5 5q31 2.87 204028_s_at RABGAP1 9q33.2-q33.3 2.86 202975_s_at RHOBTB3 5q15 2.86 202515_at DLG1 3q29 2.86 225910_at LOC284019 17q24.3 2.86 212674_s_at DHX30 3p21.31 2.86 209240_at OGT Xq13 2.86 225197_at PRO0149 16p13.2 2.86 228324_at C9orf41 9q21.13 2.86 213465_s_at PPP1R7 2q37.3 2.85 51200_at FLJ20850 19p13.11 2.85 235791_x_at CHD1 5q15-q21 2.85 208754_s_at NAP1L1 12q21.2 2.85 221476_s_at RPL15 3p24.2 2.85 226732_at RBM33 7q36.3 2.85 213504_at COPS6 7q22.1 2.85 211987_at TOP2B 3p24 2.85 200630_x_at SET 9q34 2.85 223553_s_at DOK3 5q35.3 2.84 236265_at SP4 7p15.3 2.84 227277_at LYRIC 8q22.1 2.84 202757_at COBRA1 9q34 2.84 231870_s_at CGI-07 3q26.1 2.84 224187_x_at HSPA8 11q24.1 2.84 211929_at HNRPA3 2q31.2 2.84 200004_at EIF4G2 11p15 2.84 225552_x_at AURKAIP1 1p36.33 2.83 203497_at PPARBP 17q12-q21.1 2.83 221481_x_at HNRPD 4q21.1-q21.2 2.83 227110_at HNRPC 14q11.2 2.83 202102_s_at BRD4 19p13.1 2.83 217807_s_at GLTSCR2 19q13.3 2.83 203255_at FBXO11 2p16.3 2.83 238559_at — 02 2.83 202846_s_at PIGC 1q23-q25 2.83 217774_s_at HSPC152 11q13.1 2.82 201584_s_at DDX39 19p13.12 2.82 201738_at GC20 3p22.1 2.82 200058_s_at ASCC3L1 2q11.2 2.82 200650_s_at LDHA 11p15.4 2.81 225343_at TMED8 14q24.3 2.81 201013_s_at PAICS 4pter-q21 2.81 225813_at MNAB 9q34 2.81 200621_at CSRP1 1q32 2.80 223155_at HDHD2 18q21.1 2.80 222990_at UBQLN1 9q22|9q21.2-q21.3 2.80 209836_x_at BOLA2 16p11 2.80 208598_s_at HUWE1 Xp11.22 2.79 235675_at DHFRL1 3q11.2 2.79 217987_at NS3TP1 2p24.3-q21.3 2.79 223140_s_at DHX36 03 2.79 214785_at VPS13A 9q21 2.79 224413_s_at TM2D2 8p11.23 2.79 201664_at SMC4L1 3q26.1 2.79 210149_s_at ATP5H 17q25 2.79 212195_at IL6ST 5q11 2.79 205442_at MFAP3L 4q32.3 2.79 228167_at KLHL6 03 2.78 219081_at ANKHD1 5q31.2 2.78 224575_at C3orf10 3p25.3 2.78 213165_at CAP350 1p36.13-q41 2.78 217946_s_at SAE1 19q13.32 2.78 200896_x_at HDGF 1q21-q23 2.78 214170_x_at FH 1q42.1 2.78 212223_at IDS Xq28 2.78 201441_at COX6B1 19q13.1 2.78 218085_at CHMP5 9p13.3 2.78 206176_at BMP6 6p24-p23 2.78 222579_at UBE1DC1 3q22.1 2.78 231045_x_at C11orf31 11q12.1 2.77 214328_s_at HSPCA 14q32.33 2.77 235401_s_at FCRLM1 1q23.3 2.77 228541_x_at — 15q26.1 2.77 213377_x_at RPS12 6q23.2 2.77 201232_s_at PSMD13 11p15.5 2.77 204949_at ICAM3 19p13.3-p13.2 2.77 204009_s_at KRAS 12p12.1 2.76 226414_s_at ANAPC11 17q25.3 2.76 235061_at PPM1K 4q22.1 2.76 215179_x_at PGF 14q24-q31 2.76 227052_at LOC201895 4p14 2.76 209815_at PTCH 9q22.3 2.76 210501_x_at EIF3S12 19q13.2 2.76 222984_at PAIP2 5q31.2 2.75 203985_at ZNF212 7q36.1 2.75 211763_s_at UBE2B 5q23-q31 2.75 226158_at DRE1 3q27.1 2.75 200016_x_at HNRPA1 12q13.1 2.75 200904_at HLA-E 6p21.3 2.75 56919_at WDR48 3p21.33 2.75 202761_s_at SYNE2 14q23.2 2.75 200853_at H2AFZ 4q24 2.75 203110_at PTK2B 8p21.1 2.75 218646_at FLJ20534 4q33 2.74 200966_x_at ALDOA 16q22-q24 2.74 214665_s_at CHP 15q13.3 2.74 230006_s_at DKFZp313A2432 11p14.2 2.74 226148_at BTBD15 11q24.3 2.74 209274_s_at HBLD2 9q21.33 2.74 217801_at ATP5E 20q13.32 2.73 225052_at MGC14327 9q34.3 2.73 225893_at — 01 2.73 201477_s_at RRM1 11p15.5 2.73 229588_at DNAJC10 2q32.1 2.73 203243_s_at PDLIM5 4q22 2.73 217028_at CXCR4 2q21 2.73 214683_s_at CLK1 2q33 2.72 204500_s_at AGTPBP1 9q21.33 2.72 207132_x_at PFDN5 12q12 2.72 211939_x_at BTF3 5q13.2 2.72 225469_at LOC144363 12p12.1 2.72 219043_s_at PDCL3 /// LOC285359 2q11.2 /// 3q12.3 2.71 202233_s_at UQCRH 1p34.1 2.71 225640_at LOC401504 9p13.2 2.71 226316_at — 13 2.71 214709_s_at KTN1 /// PDIA6 14q22.1 /// 2p25.1 2.71 211974_x_at RBPSUH 4p15.2 2.71 201993_x_at HNRPDL 4q13-q21 2.71 204805_s_at H1FX 3q21.3 2.71 1560587_s_at PRDX5 11q13 2.71 225786_at FAM36A 1q44 2.71 233642_s_at KIAA1414 2p22.2 2.71 224852_at TTC17 11p12-p11.2 2.71 213735_s_at COX5B 2cen-q13 2.71 209509_s_at DPAGT1 11q23.3 2.71 209435_s_at ARHGEF2 1q21-q22 2.71 201204_s_at RRBP1 20p12 2.70 212245_at MCFD2 2p21 2.70 224876_at FLJ37562 5q31.1 2.70 223547_at C14orf100 14q23.1 2.70 209104_s_at NOLA2 5q35.3 2.70 210825_s_at PBP 12q24.23 2.70 201227_s_at NDUFB8 10q23.2-q23.33 2.70 214431_at GMPS 3q24 2.70 232843_s_at DOCK8 9p24.3 2.70 219563_at C14orf139 14q32.13 2.70 203593_at CD2AP 6p12 2.70 227964_at FKSG44 11q13 2.69 239468_at C10orf48 10p12.1 2.69 220942_x_at E2IG5 3q21.1 2.69 206860_s_at FLJ20323 7p22-p21 2.69 200826_at SNRPD2 19q13.2 2.69 224814_at DPP7 9q34.3 2.69 238604_at — 07 2.69 223051_at SSU72 1p36.33 2.69 226816_s_at KIAA1143 3p21.31 2.69 219028_at HIPK2 7q32-q34 2.69 224977_at — 06 2.68 200746_s_at GNB1 1p36.33 2.68 209181_s_at RABGGTB 1p31 2.68 208863_s_at SFRS1 17q21.3-q22 2.68 217716_s_at SFC61A1 3q21.3 2.68 210137_s_at DCTD 4q35.1 2.68 215416_s_at STOML2 9p13.1 2.68 207358_x_at MACF1 1p32-p31 2.68 231059_x_at SCAND1 20q11.1-q11.23 2.68 234762_x_at NLN 5q12.3 2.67 220948_s_at ATP1A1 1p21 2.67 212513_s_at USP33 1p31.1 2.67 217756_x_at SERF2 15q15.3 2.67 225539_at ZNF295 21q22.3 2.67 202373_s_at RAB3-GAP150 1q41 2.67 201472_at VBP1 Xq28 2.66 201922_at TINP1 5q13.3 2.66 221654_s_at USP3 15q22.3 2.66 222825_at CGI-77 8q21.3 2.66 211954_s_at RANBP5 13q32.2 2.66 237367_x_at CFLAR 2q33-q34 2.66 213743_at CCNT2 2q21.3 2.66 202906_s_at NBN 8q21 2.66 208993_s_at PPIG 2q31.1 2.66 202177_at GAS6 13q34 2.66 218580_x_at AURKAIP1 1p36.33 2.65 225658_at LOC339745 2q22.1 2.65 203391_at FKBP2 11q13.1-q13.3 2.65 219922_s_at LTBP3 11q12 2.65 214629_x_at RTN4 2p16.3 2.65 222449_at TMEPAI 20q13.31-q13.33 2.65 204279_at PSMB9 6p21.3 2.65 208788_at ELOVL5 6p21.1-p12.1 2.65 225220_at — 04 2.65 209224_s_at NDUFA2 5q31 2.65 225011_at PRKAR2A 3p21.3-p21.2 2.65 216348_at RPS17 /// LOC402057 15q /// 22q12.3 2.65 217827_s_at SPG21 15q21-q22 2.65 225302_at TXNDC10 18q22 2.64 214214_s_at C1QBP 17p13.3 2.64 200869_at RPL18A /// LOC390354 19p13 2.64 208764_s_at ATP5G2 12q13.13 2.64 223096_at NOP5/NOP58 2q33.1 2.64 201757_at NDUFS5 1p34.2-p33 2.64 209669_s_at PAI-RBP1 1p31 2.64 224915_x_at TALDO1 /// HSUP1 11p15.5-p15.4 /// 20q13.13 2.64 212297_at ATP13A3 3q29 2.64 203658_at SLC25A20 3p21.31 2.64 220939_s_at DPP8 15q22 2.64 225460_at SEC22L3 3p22.1 2.64 217945_at BTBD1 15q24 2.64 202693_s_at STK17A 7p12-p14 2.63 212251_at MTDH 8q22.1 2.63 225971_at DDHD1 14q21 2.63 225110_at FLJ10826 16q12.2 2.63 219293_s_at PTD004 2q31.1 2.63 224688_at FLJ10099 7q11.21 2.63 200905_x_at HLA-E 6p21.3 2.63 200909_s_at RPLP2 11p15.5-p15.4 2.63 219366_at AVEN 15q13.1 2.63 207335_x_at ATP51 4p16.3 2.63 219079_at CYB5R4 6pter-q22.33 2.63 209476_at TXNDC 14q22.1 2.63 226361_at TMEM42 3p21.31 2.63 213571_s_at EIF4E2 2q37.1 2.62 200949_x_at RPS20 8q12 2.62 210466_s_at PAI-RBP1 1p31 2.62 212386_at TCF4 18q21.1 2.62 204744_s_at IARS 9q21 2.62 222728_s_at MGC5306 11q21 2.62 204076_at ENTPD4 8p21.3 2.62 212038_s_at VDAC1 5q31 2.62 202692_s_at UBTF 17q21.3 2.61 222472_at AFTIPHILIN 2p14 2.61 227369_at PAI-RBP1 1p31 2.61 210793_s_at NUP98 11p15.5 2.61 208798_x_at GM88 15q11.2 2.61 201653_at CNIH 14q22.2 2.61 219598_s_at RWDD1 6q13-q22.33 2.61 221474_at MRLC2 18p11.31 2.61 200674_s_at RPL32 3p25-p24 2.61 200846_s_at PPP1CA 11q13 2.61 217722_s_at NGRN 15q26.1 2.61 229429_x_at — 1q21.1 2.61 213034_at KIAA0999 11q23.3 2.61 210183_x_at — 14 2.60 225515_s_at LOC220906 10p12.1 2.60 202117_at ARHGAP1 11p12-q12 2.60 224677_x_at C11orf31 11q12.1 2.60 211275_s_at GYG 3q24-q25.1 2.60 211475_s_at BAG1 9p12 2.60 200819_s_at RPS15 19p13.3 2.60 218126_at FAM82C 15q15.1 2.60 217805_at ILF3 19p13.2 2.60 217836_s_at YY1AP1 1q22 2.60 224481_s_at HECTD1 14q12 2.59 200805_at LMAN2 5q35.3 2.59 203667_at TBCA 5q14.1 2.59 202413_s_at USP1 1p31.3 2.59 200888_s_at RPL23 17q 2.59 201385_at DHX15 4p15.3 2.59 210024_s_at UBE2E3 2q32.1 2.59 215127_s_at RBMS1 2q24.2 2.59 225001_at RAB3D 19p13.2 2.59 224784_at MLLT6 17q21 2.58 216028_at DKFZP564C152 11 2.58 203566_s_at AGL 1p21 2.58 225634_at ZC3HAV1 7q34 2.58 202613_at CTPS 1p34.1 2.58 226748_at LYSMD2 15q21.2 2.58 219192_at UBAP2 9p13.3 2.58 225182_at TMEM50B 21q22.11 2.58 221046_s_at HSPC135 3q13.2 2.58 208883_at EDD1 8q22 2.58 233849_s_at ARHGAP5 14q12 2.57 213398_s_at C14orf124 14q11.2 2.57 202230_s_at CHERP 19p13.1 2.57 207641_at TNFRSF13B 17p11.2 2.57 203024_s_at C5orf15 5q31.1 2.57 225395_s_at C9orf10OS 9q22.31 2.57 209248_at GHITM 10q23.1 2.57 219041_s_at REPIN1 7q36.1 2.57 201175_at TMX2 11cen-q22.3 2.57 223133_at TMEM14B 6p25.1-p23 2.57 218917_s_at ARID1A 1p35.3 2.57 217877_s_at GPBP1L1 1p34.1 2.56 218495_at UXT Xp11.23-p11.22 2.56 208687_x_at HSPA8 11q24.1 2.56 227196_at RHPN2 19q13.11 2.56 200073_s_at HNRPD 4q21.1-q21.2 2.56 205047_s_at ASNS 7q21.3 2.56 203501_at PGCP 8q22.2 2.56 229498_at — X 2.55 222405_at — 15 2.55 220741_s_at PPA2 4q25 2.55 226481_at VprBP 3p21.2 2.55 225845_at BTBD15 11q24.3 2.55 203217_s_at ST3GAL5 2p11.2 2.55 202343_x_at COX5B 2cen-q13 2.55 235398_at LOC390980 19q13.43 2.55 201703_s_at PPP1R10 6p21.3 2.55 219123_at ZNF232 17p13-p12 2.55 225405_at DKFZp762N1910 11q12.3 2.54 209153_s_at TCF3 19p13.3 2.54 213890_x_at RPS16 19q13.1 2.54 226921_at UBR1 15q13 2.54 211458_s_at GABARAPL1 /// GABARAPL3 12p13.2 /// 15q26.1 2.54 230379_x_at PRO1853 2p22.2 2.54 243496_at — 10 2.54 225017_at CCDC14 3q21.1 2.54 222785_x_at C11orf1 11q13-q22 2.54 223857_x_at LOC51234 15q14 2.54 200749_at RAN /// LOC391717 12q24.3 /// 4q34.1 2.54 226508_at PHC3 3q26.2 2.53 210968_s_at RTN4 2p16.3 2.53 201285_at MKRN1 7q34 2.53 207657_x_at TNPO1 5q13.2 2.53 202656_s_at SERTAD2 2p14 2.53 226780_s_at HSPC268 7q34 2.53 224780_at RBM17 10p15.1 2.53 205590_at RASGRP1 15q15 2.53 212502_at C10orf22 10q21.3 2.53 201106_at GPX4 19p13.3 2.53 221743_at CUGBP1 11p11 2.53 227611_at TARSL2 15q26.3 2.53 228562_at ZBTB10 8q13-q21.1 2.53 225725_at — 03 2.52 210996_s_at YWHAE 17p13.3 2.52 211378_x_at PPIA 7p13-p11.2 2.52 208714_at NDUFV1 11q13 2.52 211025_x_at COX5B 2cen-q13 2.52 208688_x_at EIF3S9 7p22.3 2.52 212614_at ARID5B 10q21.2 2.52 201433_s_at PTDSS1 8q22 2.52 227979_at — 11 2.52 217944_at POMGNT1 1p34.1 2.52 223269_at POLR3GL 1q21.1 2.52 225086_at FLJ38426 15q14 2.52 226450_at INSR 19p13.3-p13.2 2.52 227932_at — 03 2.51 226131_s_at RPS16 19q13.1 2.51 208783_s_at MCP 1q32 2.51 207922_s_at MAEA 4p16.3 2.51 221974_at SNRPN 15q11.2 2.51 202066_at PPFIA1 11q13.3 2.51 213476_x_at TUBB3 16q24.3 2.51 1555961_a_at HINT1 5q31.2 2.50 213687_s_at RPL35A 3q29-qter 2.50 203845_at PCAF 3p24 2.50 211787_s_at EIF4A1 17p13 2.50 225133_at KLF3 4p14 2.50 227548_at ORMDL1 02 2.50 211711_s_at PTEN 10q23.3 2.50 204992_s_at PFN2 3q25.1-q25.2 2.50 227651_at BTBD14B 19p13.13 2.50 226227_x_at TALDO1 /// HSUP1 11p15.5-p15.4 /// 20q13.13 2.50 210646_x_at RPL13A 19q13.3 2.50 204774_at EVI2A 17q11.2 2.50 229434_at HNRPD 4q21.1-q21.2 2.50 228049_x_at — 16 2.50 200048_s_at JTB 1q21 2.50 53720_at FLJ11286 19p13.2 2.50 200029_at RPL19 17q11.2-q12 2.50 214626_s_at GANAB 11q12.3 2.50 219133_at KS 3p24.2 2.49 200847_s_at TMEM66 8p12 2.49 202536_at CHMP2B 3p12.1 2.49 218482_at ENY2 8q23.1 2.49 218188_s_at TIMM13 19p13.3 2.49 201797_s_at VARS 6p21.3 2.49 208190_s_at LISCH7 19q13.12 2.49 202724_s_at FOXO1A 13q14.1 2.49 200037_s_at CBX3 7p15.2 2.49 226835_s_at TALDO1 /// HSUP1 11p15.5-p15.4 /// 20q13.13 2.49 226300_at MED19 11q12.1 2.49 228454_at MLR2 10q24 2.49 224782_at ZMAT2 5q31.3 2.49 224948_at MRPS24 7p14 2.49 224840_at FKBP5 6p21.3-21.2 2.48 225583_at UXS1 2q12.2 2.48 47608_at TJAP1 6p21.1 2.48 200027_at NARS 18q21.2-q21.3 2.48 222421_at UBE2H 7q32 2.48 201486_at RCN2 15q23 2.48 209533_s_at PLAA 9p21 2.47 213918_s_at NIPBL 5p13.2 2.47 218007_s_at RPS27L 15q22.2 2.47 209377_s_at HMGN3 6q14.1 2.47 212498_at MARCH-VI 5p15.2 2.47 205267_at POU2AF1 11q23.1 2.47 225916_at ZNF131 5p12-p11 2.47 200912_s_at EIF4A2 3q28 2.47 235450_at FBXL4 6q16.1-q16.3 2.47 201183_s_at CHD4 12p13 2.47 203380_x_at SFRS5 14q24 2.47 217947_at CKLFSF6 3p23 2.47 202060_at SH2BP1 11p15.3 2.47 217092_x_at RPL7 /// LOC90193 /// 8q21.11 /// 12p12.3 /// 2.47 LOC388401 /// LOC389305 /// 17q21.33 /// 5q14.1 /// LOC392550 /// LOC439954 Xq26.3 /// 10p11.21 200964_at UBE1 Xp11.23 2.47 235457_at MAML2 11q21 2.47 200095_x_at RPS10 6p21.31 2.46 202227_s_at BRD8 5q31 2.46 225606_at BCL2L11 2q13 2.46 216241_s_at TCEA1 8q11.2 2.46 200010_at RPL11 1p36.1-p35 2.46 201845_s_at RYBP 3p13 2.46 226134_s_at MSI2 17q23.2 2.46 202521_at CTCF 16q21-q22.3 2.46 219620_x_at FLJ20245 9q34.3 2.46 223136_at AIG1 6q24.2 2.46 213065_at MGC23401 12q21.1 2.45 208752_x_at NAP1L1 12q21.2 2.45 201997_s_at SPEN 1p36.33-p36.11 2.45 203033_x_at FH 1q42.1 2.45 209511_at POLR2F 22q13.1 2.45 200033_at DDX5 17q21 2.45 212847_at NEXN 1p31.1 2.45 217816_s_at PCNP 3q12.3 2.45 222839_s_at PAPOLG 2p16.1 2.45 222494_at CHES1 14q24.3-q32.11 2.45 201412_at LRP10 14q11.2 2.45 201592_at EIF3S3 8q24.11 2.45 214042_s_at RPL22 1p36.3-p36.2 2.45 217869_at HSD17B12 11p11.2 2.45 203668_at MAN2C1 15q11-q13 2.45 202029_x_at RPL38 17q23-q25 2.45 201384_s_at NBR1 17q21.1 2.44 204236_at FLI1 11q24.1-q24.3 2.44 224651_at C10orf9 10p11.21 2.44 212302_at RTF1 15q15.1 2.44 223808_s_at PTPMT1 11p11.2 2.44 222683_at RNF20 9q22 2.44 222745_s_at C15orf29 15q14 2.44 202909_at EPM2AIP1 3p22.1 2.44 212867_at NCOA2 8q13.3 2.44 220046_s_at CCNL1 3q25.31 2.44 209492_x_at ATP5I 4p16.3 2.44 226884_at LRRN1 3p26.2 2.44 225621_at ALG2 9q22.33 2.43 200667_at UBE2D3 4q24 2.43 218290_at PLEKHJ1 19p13.3 2.43 225314_at OCIAD2 4p12 2.43 200763_s_at RPLP1 15q22 2.43 224729_s_at ATPAF1 1p33-p32.3 2.43 225281_at C3orf17 3q13.2 2.43 230650_at — 08 2.43 203406_at MFAP1 15q15-q21 2.43 200091_s_at RPS25 11q23.3 2.42 226165_at LOC401466 8q21.2 2.42 214096_s_at SHMT2 12q12-q14 2.42 200815_s_at PAFAH1B1 17p13.3 2.42 218680_x_at HYPK 15q15.3 2.42 201501_s_at GRSF1 4q13 2.42 232075_at REC14 15q25.1 2.42 212709_at NUP160 11p11.2 2.42 225945_at ZNF655 7q22.1 2.42 200814_at PSME1 14q11.2 2.42 218082_s_at UBP1 3p23 2.42 209065_at UQCRB 8q22 2.42 213483_at PPWD1 5q12.3 2.42 228446_at KIAA2026 9p24.1 2.42 213313_at RABGAP1 9q33.2-q33.3 2.41 208837_at TMED3 15q24-q25 2.41 215191_at FBXL11 11q13.2 2.41 200081_s_at RPS6 9p21 2.41 224558_s_at MALAT1 11q13.1 2.41 210962_s_at AKAP9 7q21-q22 2.41 218242_s_at SUV420H1 11q13.2 2.41 234295_at DBR1 3q22.3 2.41 226334_s_at AHSA2 2p15 2.41 1555764_s_at TIMM10 11q12.1-q12.3 2.41 214022_s_at IFITM1 11p15.5 2.41 212790_x_at RPL13A 19q13.3 2.41 201572_x_at DCTD 4q35.1 2.41 228960_at NARG2 15q22.2 2.41 229666_s_at CSTF3 11p13 2.41 218807_at VAV3 1p13.3 2.41 200752_s_at CAPN1 11q13 2.40 218008_at FLJ10099 7q11.21 2.40 227755_at — 17 2.40 201622_at SND1 7q31.3 2.40 201986_at THRAP1 17q22-q23 2.40 218982_s_at MRPS17 7p11 2.40 208673_s_at SFRS3 6p21 2.40 201448_at TIA1 2p13 2.40 225835_at SLC12A2 5q23.3 2.40 217846_at QARS 3p21.3-p21.1 2.40 213027_at SSA2 1q31 2.40 202221_s_at EP300 22q13.2 2.40 225964_at ZXDC 3q21.2 2.39 213511_s_at MTMR1 Xq28 2.39 205070_at ING3 7q31 2.39 218117_at RBX1 22q13.2 2.39 217866_at FLJ12529 11q12.2 2.39 218116_at C9orf78 9q34.11 2.38 218025_s_at PECI 6p24.3 2.38 201948_at GNL2 1p34.3 2.38 201628_s_at RRAGA 9p22.1 2.38 218020_s_at TEX27 6pter-p22.3 2.38 201366_at ANXA7 10q21.1-q21.2 2.38 202032_s_at MAN2A2 15q26.1 2.38 217837_s_at VPS24 2p24.3-p24.1 2.37 218258_at POLR1D 13q12.2 2.37 200817_x_at RPS10 6p21.31 2.37 202704_at TOB1 17q21 2.37 222447_at DREV1 16p13-p12 2.37 207522_s_at ATP2A3 17p13.3 2.37 207467_x_at CAST 5q15-q21 2.37 200812_at CCT7 2p13.2 2.37 212476_at CENTB2 3q29 2.37 218919_at ZFAND1 8q21.13 2.37 53968_at KIAA1698 11q12.3 2.36 202077_at NDUFAB1 16p12.1 2.36 201561_s_at CLSTN1 1p36.22 2.36 221842_s_at ZNF131 5p12-p11 2.36 204396_s_at GRK5 10q24-qter 2.36 220925_at MAK10 9q21.33 2.36 220643_s_at FAIM 3q22.3 2.36 203330_s_at STX5A 11q12.3 2.35 211257_x_at ZNF638 2p13.2-p13.1 2.35 201687_s_at API5 11p12-q12 2.35 202708_s_at HIST2H2BE 1q21-q23 2.35 204215_at C7orf23 7q21.1-q21.2 2.35 218396_at VPS13C 15q22.2 2.35 225243_s_at SLMAP 3p21.2-p14.3 2.35 212904_at LRRC47 1p36.32 2.35 217898_at C15orf24 15q14 2.35 218712_at C1orf109 1p34.3 2.35 227533_at — 01 2.34 201737_s_at 6-Mar 5p15.2 2.34 214179_s_at NFE2L1 17q21.3 2.34 212933_x_at RPL13 16q24.3|17p11.2 2.34 202171_at ZNF161 17q23.2 2.34 209515_s_at RAB27A 15q15-q21.1 2.34 208737_at ATP6V1G1 9q32 2.34 227162_at ZBTB26 9q33.2 2.34 216308_x_at GRHPR 9q12 2.34 38892_at KIAA0240 6p21.1 2.33 213037_x_at STAU 20q13.1 2.33 226954_at UBE2R2 9p13.3 2.33 224858_at ZDHHC5 11q12.1 2.33 202778_s_at ZNF198 13q11-q12 2.33 218611_at IER5 1q25.3 2.33 235158_at FLJ14803 7q32.2 2.33 219286_s_at RBM15 1p13 2.33 215884_s_at UBQLN2 Xp11.23-p11.1 2.33 220924_s_at SLC38A2 12q 2.33 212140_at SCC-112 4p14 2.33 213811_x_at TCF3 19p13.3 2.33 226821_at RIF1 2q23.3 2.33 212191_x_at RPL13 16q24.3|17p11.2 2.32 234107_s_at HARS2 20p11.23 2.32 221425_s_at HBLD2 9q21.33 2.32 211542_x_at RPS10 6p21.31 2.32 225512_at ZBTB38 3q23 2.32 213203_at SNAPC5 15q22.31 2.32 203663_s_at COX5A 15q25 2.32 203062_s_at MDC1 6pter-p21.31 2.32 225107_at HNRPA2B1 7p15 2.32 223184_s_at AGPAT3 21q22.3 2.32 221510_s_at GLS 2q32-q34 2.31 218932_at C1orf181 1p22.3 2.31 201139_s_at SSB 2q31.1 2.31 200716_x_at RPL13A 19q13.3 2.31 201113_at TUFM 16p11.2 2.31 217719_at EIF3S6IP 22q 2.31 213408_s_at PIK4CA /// LOC220686 22q11.21 /// 22q11.22 2.31 200025_s_at RPL27 17q21.1-q21.2 2.31 209630_s_at FBXW2 9q34 2.31 211765_x_at PPIA 7p13-p11.2 2.31 218961_s_at PNKP 19q13.3-q13.4 2.31 200653_s_at CALM1 14q24-q31 2.30 202475_at NIFIE14 19q13.1 2.30 223062_s_at PSAT1 9q21.2 2.30 203082_at BMS1L 10q11.21 2.30 200092_s_at RPL37 5p13 2.30 223009_at FLJ20625 11q13.4 2.30 207435_s_at SRRM2 16p13.3 2.30 225530_at MOBKL2A 19p13.3 2.30 202754_at R3HDM 2q21.3 2.30 218104_at TEX10 9q31.1 2.30 201934_at PRO2730 3p21.2 2.30 226845_s_at MYEOV2 2q37.3 2.30 201023_at TAF7 5q31 2.30 208753_s_at NAP1L1 12q21.2 2.30 225176_at — 05 2.30 225573_at FLJ12592 3q22.1 2.30 211285_s_at UBE3A 15q11-q13 2.30 241348_at ZNF654 3p11.1 2.30 224648_at GPBP1 5q11.2 2.29 223211_at HPCL2 3p25.1 2.29 222490_at POLR3E 16p12.1 2.29 200074_s_at RPL14 /// RPL14L 3p22-p21.2 /// 12q14.2 2.29 211503_s_at RAB14 9q32-q34.11 2.29 212215_at PREPL 2p22.1 2.29 202603_at ADAM10 15q2 2.29 224705_s_at TNRC6A 16p11.2 2.28 204373_s_at CAP350 1p36.13-q41 2.28 1554067_at FLJ32549 12q14.2 2.28 202325_s_at ATP5J 21q21.1 2.28 224735_at CYBASC3 11q12.2 2.28 208766_s_at HNRPR 1p36.12 2.28 203259_s_at C6orf74 6q13-q24.3 2.28 202605_at GUSB 7q21.11 2.28 212537_x_at RPL17 18q21 2.27 201194_at SEPW1 19q13.3 2.27 222443_s_at RBM8A 1q12 2.27 200768_s_at MAT2A 2p11.2 2.27 225073_at PPHLN1 12q12 2.27 212824_at FUBP3 9q34.2 2.27 201546_at TRIP12 2q36.3 2.27 201928_at PKP4 2q23-q31 2.27 228652_at FLJ38288 19q13.43 2.27 48580_at CXXC1 18q12 2.27 211509_s_at RTN4 2p16.3 2.27 214657_s_at TncRNA 11q13.1 2.27 203165_s_at SLC33A1 3q25.31 2.27 201931_at ETFA 15q23-q25 2.27 235615_at PGGT1B 5q22.3 2.27 226859_at bA16L21.2.1 9q31.3 2.27 218011_at UBL5 19p13.3 2.27 202297_s_at RER1 1pter-q24 2.27 218409_s_at DNAJC1 10p12.31 2.27 200936_at RPL8 8q24.3 2.27 208683_at CAPN2 1q41-q42 2.27 213698_at ZNF258 1p34.2 2.27 210275_s_at ZA20D2 9q13-q21 2.27 219147_s_at C9orf95 9q21.13 2.26 224769_at — 17 2.26 225422_at CDC26 9q32 2.26 222119_s_at FBXO11 2p16.3 2.26 213704_at RABGGTB 1p31 2.26 201236_s_at BTG2 1q32 2.26 229419_at FBXW7 4q31.3 2.26 204208_at RNGTT 6q16 2.26 229519_at FXR1 3q28 2.26 226091_s_at MRFAP1 4p16.1 2.26 55872_at GM632 20q13.33 2.26 217729_s_at AES 19p13.3 2.26 202231_at hfl-B5 11p13 2.25 219206_x_at CGI-119 12q14.1-q15 2.25 201731_s_at TPR 1q25 2.25 201256_at COX7A2L 2p21 2.25 216221_s_at PUM2 2p22-p21 2.25 203040_s_at HMBS 11q23.3 2.25 213019_at RANBP6 9p24.1 2.25 213080_x_at RPL5 1p22.1 2.25 212918_at RECQL 12p12 2.25 208942_s_at TLOC1 3q26.2 2.25 1553581_s_at FLJ36754 5q12.3 2.25 200893_at SFRS10 3q26.2-q27 2.25 225115_at HIPK2 7q32-q34 2.25 200038_s_at RPL17 18q21 2.25 230178_s_at STATIP1 18q12.2 2.25 232683_s_at PARP6 15q23 2.25 201601_x_at IFITM1 11p15.5 2.25 212204_at DKFZP564G2022 15q15.1 2.24 231530_s_at C11orf1 11q13-q22 2.24 208517_x_at BTF3 5q13.2 2.24 211940_x_at H3F3A /// LOC440926 1q41 /// 2q31.1 2.24 201323_at EBNA1BP2 1p35-p33 2.24 232681_at PSIP1 9p22.3 2.24 238431_at — 02 2.24 202172_at ZNF161 17q23.2 2.24 226851_at LYPLAL1 1q41 2.24 200977_s_at TAX1BP1 7p15 2.24 233632_s_at XRN1 3q23 2.24 201479_at DKC1 Xq28 2.24 1560396_at KLHL6 03 2.23 229075_at — 04 2.23 226387_at RSBN1L 7q11.23 2.23 201304_at NDUFA5 7q32 2.23 206792_x_at PDE4C 19p13.11 2.23 218189_s_at NANS 9p24.1-p23 2.23 213941_x_at RPS7 2p25 2.23 217745_s_at MAK3 3q13.2 2.23 226628_at THOC2 Xq25-q26.3 2.23 212697_at LOC162427 17q21.2 2.23 224655_at AK3 9p24.1-p24.3 2.23 208095_s_at SRP72 4q11 2.22 221751_at PANK3 5q34 2.22 231817_at USP53 4q26 2.22 212511_at PICALM 11q14 2.22 225493_at LOC144438 12q13.12 2.22 225270_at NEO1 15q22.3-q23 2.22 209103_s_at UFD1L 22q11.21 2.22 226181_at TUBE1 6q21 2.22 205292_s_at HNRPA2B1 7p15 2.22 214039_s_at LAPTM4B 8q22.1 2.22 1559822_s_at — 08 2.22 216338_s_at YIPF3 6p21.1 2.22 201347_x_at GRHPR 9q12 2.22 214041_x_at RPL37A 2q35 2.22 202591_s_at SSBP1 7q34 2.22 225358_at DNAJC19 3q26.33 2.21 209455_at FBXW11 5q35.1 2.21 203416_at CD53 1p13 2.21 214329_x_at TNFSF10 3q26 2.21 211662_s_at VDAC2 10q22 2.21 206688_s_at CPSF4 7q22.1 2.21 225635_s_at — 9p13.2 2.21 224151_s_at AK3 9p24.1-p24.3 2.21 212296_at PSMD14 2q24.2 2.21 218152_at HMG20A 15q24 2.21 213574_s_at KPNB1 17q21.32 2.21 223622_s_at HYI 1p34.2 2.21 223350_x_at LIN7C 11p14 2.21 213701_at DKFZp434N2030 12q21.33 2.21 225403_at C9orf23 9p13.3 2.20 214047_s_at MBD4 3q21-q22 2.20 226290_at BDP1 5q12-q13 2.20 225724_at FLJ31306 14 2.20 222182_s_at CNOT2 12q15 2.20 206405_x_at USP6 17q11 2.20 228970_at ZBTB8OS 1p35.1 2.20 214177_s_at PBXIP1 1q22 2.19 212578_x_at RPS17 15q 2.19 207801_s_at RNF10 12q24.31 2.19 210046_s_at IDH2 15q26.1 2.19 218563_at NDUFA3 19q13.42 2.19 219119_at LSM8 7q31.1-q31.3 2.19 229120_s_at CDC42SE1 1q21.2 2.19 213225_at PPM1B 2p21 2.19 210951_x_at RAB27A 15q15-q21.1 2.19 201864_at GDI1 Xq28 2.19 225823_at QIL1 19p13.3 2.19 214363_s_at MATR3 5q31.2 2.19 200788_s_at PEA15 1q21.1 2.19 213828_x_at H3F3A /// LOC440926 1q41 /// 2q31.1 2.19 201987_at THRAP1 17q22-q23 2.19 231714_s_at AP4B1 1p13.2 2.18 212036_s_at PNN 14q21.1 2.18 208716_s_at TMCO1 1q22-q25 2.18 209695_at PTP4A3 8q24.3 2.18 223576_at C6orf203 6q21 2.18 200036_s_at RPL10A 6p21.3-p21.2 2.18 228318_s_at FLJ34443 4p16.3 2.18 227677_at JAK3 19p13.1 2.18 203707_at ZNF263 16p13.3 2.18 204246_s_at DCTN3 9p13 2.18 230742_at — 03 2.18 202431_s_at MYC 8q24.12-q24.13 2.18 57082_at LDLRAP1 1p36-p35 2.18 212378_at GART 21q22.1|21q22.11 2.18 205022_s_at CHES1 14q24.3-q32.11 2.18 203285_s_at HS2ST1 1p31.1-p22.1 2.17 228768_at KIAA1961 5q23.3 2.17 226277_at COL4A3BP 5q13.3 2.17 200066_at IK 2p15-p14|5q31.3 2.17 201293_x_at PPIA 7p13-p11.2 2.17 209066_x_at UQCRB 8q22 2.17 212455_at YT521 4q13.2 2.17 200920_s_at BTG1 12q22 2.17 227765_at — 08 2.17 223068_at EML4 2p22-p21 2.17 201406_at RPL36A Xq22.1 2.17 225083_at C6orf51 6q21 2.17 212699_at SCAMP5 15q23 2.17 204053_x_at PTEN 10q23.3 2.17 214080_x_at PRKCSH 19p13.2 2.17 242606_at — 2.17 229711_s_at MGC5370 12q14.3 2.16 219869_s_at SLC39A8 4q22-q24 2.16 226538_at MAN2A1 5q21-q22 2.16 201528_at RPA1 17p13.3 2.16 201290_at SEC11L1 15q25.3 2.16 239629_at CFLAR 2q33-q34 2.16 200021_at CFL1 11q13 2.16 221897_at TRIM52 5q35.3 2.16 209448_at HTATIP2 11p15.1 2.16 226511_at — 09 2.16 224867_at C1orf151 1p36.13 2.16 210908_s_at PFDN5 12q12 2.16 235427_at — 02 2.16 212802_s_at GAPVD1 9q33.3 2.16 201641_at BST2 19p13.2 2.16 212536_at ATP11B 3q27 2.16 225967_s_at LOC284184 17q25.3 2.16 212082_s_at MYL6 12q13.2 2.16 228751_at CLK4 5q35 2.16 212010_s_at H41 3q22.1 2.16 35974_at LRMP 12p12.1 2.15 212270_x_at RPL17 18q21 2.15 222423_at NDFIP1 5q31.3 2.15 217802_s_at NUCKS1 1q32.1 2.15 201254_x_at RPS6 9p21 2.15 225509_at LOC56757 5q31-q32 2.15 210705_s_at TRIM5 11p15 2.15 208718_at DDX17 22q13.1 2.15 229410_at PAEP 9q34 2.15 200657_at SLC25A5 Xq24-q26 2.15 225332_at KRTAP4-7 17q12-q21 2.15 222986_s_at SCOTIN 3p21.31 2.15 220746_s_at RAP80 5q35.2 2.15 221522_at ANKRD27 19q13.11 2.14 202688_at TNFSF10 3q26 2.14 224890_s_at LOC389541 7q22.1 2.14 212534_at ZNF24 18q12 2.14 222229_x_at RPL26 /// LOC391126 /// 17p13 /// 1q24.1 /// 2.14 LOC392501 /// LOC400055 /// Xq21.31 /// 12q21.31 /// LOC441073 /// LOC441533 5q11.2 /// Yp11.2 201558_at RAE1 20q13.32 2.14 214152_at PIGB 15q21-q22 2.14 218852_at C14orf10 14q13.2 2.14 218048_at COMMD3 10pter-q22.1 2.14 201409_s_at PPP1CB 2p23 2.14 212483_at NIPBL 5p13.2 2.14 200015_s_at 2-Sep 2q37 2.14 203513_at FLJ21439 15q14 2.14 222533_at CRBN 3p26.2 2.14 209563_x_at CALM1 14q24-q31 2.13 208909_at UQCRFS1 19q12-q13.1 2.13 226923_at SCFD2 4q12 2.13 225260_s_at MRPL32 7p14 2.13 224692_at PPP1R15B 1q32.1 2.13 226831_at LOC91137 5q22.1 2.13 212060_at SR140 3q23 2.13 213603_s_at RAC2 22q13.1 2.13 221493_at TSPYL1 6q22-q23 2.13 217939_s_at AFTIPHILIN 2p14 2.12 200704_at LITAF 16p13.13 2.12 225763_at RCSD1 1q22-q24 2.12 213754_s_at PAIP1 /// LOC388345 5p12 /// 17p11.2 2.12 223005_s_at C9orf5 9q31 2.12 212661_x_at PPIA 7p13-p11.2 2.11 201244_s_at RAF1 3p25 2.11 230669_at RASA2 3q22-q23 2.11 207040_s_at ST13 22q13.2 2.11 221865_at C9orf91 9q32 2.11 223682_s_at MGC11102 11q13.1 2.11 224675_at MESDC2 15q13 2.11 214662_at WDR43 2p23.2 2.11 226426_at ADNP 20q13.13 2.11 208768_x_at RPL22 1p36.3-p36.2 2.10 213361_at TDRD7 9q22.33 2.10 226140_s_at OTUD1 10p12.31 2.10 225927_at MAP3K1 5q11.2 2.10 202659_at PSMB10 16q22.1 2.10 208979_at NCOA6 20q11 2.10 202519_at MONDOA 12q21.31 2.10 224561_s_at MORF4L1 15q24 2.10 201762_s_at PSME2 14q11.2 2.10 208655_at CCNI 4q21.1 2.10 227525_at GLCCI1 7p21.3 2.10 227132_at LOC51123 8q22.3 2.10 208610_s_at SRRM2 16p13.3 2.10 217398_x_at GAPDH 12p13 2.10 211978_x_at PPIA 7p13-p11.2 2.09 225112_at ABI2 2q33 2.09 209084_s_at RAB28 4p15.33 2.09 227346_at ZNFN1A1 7p13-p11.1 2.09 218740_s_at CDK5RAP3 17q21.32 2.09 200976_s_at TAX1BP1 7p15 2.09 216652_s_at DR1 1p22.1 2.09 208809_s_at C6orf62 6p22.2 2.09 209648_x_at SOCS5 2p21 2.09 203200_s_at MTRR 5p15.3-p15.2 2.09 201381_x_at CACYBP 1q24-q25 2.08 203028_s_at CYBA 16q24 2.08 213101_s_at ACTR3 2q14.1 2.08 201060_x_at STOM 9q34.1 2.08 200963_x_at RPL31 2q11.2 2.08 226652_at USP3 15q22.3 2.08 213786_at — 07 2.08 227499_at — 08 2.08 224755_at SMBP 10q24.1 2.08 212914_at CBX7 22q13.1 2.08 214288_s_at PSMB1 6q27 2.08 212242_at TUBA1 2q35 2.08 229513_at STRBP 9q33.3 2.08 202395_at NSF 17q21 2.08 234873_x_at RPL7A /// LOC133748 /// 9q34 /// 5q14.1 /// 18q12.2-q12.3 2.08 LOC388474 222982_x_at SLC38A2 12q 2.08 201930_at MCM6 2q21 2.08 201782_s_at AIP 11q13.3 2.08 217961_at FLJ20551 3p22.2 2.08 200994_at IPO7 11p15.4 2.08 220306_at FAM46C 1p12 2.08 1569349_at C11orf30 11q13.5 2.07 201318_s_at MRCL3 /// MRLC2 18p11.31 2.07 210588_x_at HNRPH3 10q22 2.07 203943_at KIF3B 20q11.21 2.07 221652_s_at C12orf11 12p11.23 2.07 232511_at RANBP2L1 2q13 2.07 221726_at RPL22 1p36.3-p36.2 2.07 215671_at PDE4B 1p31 2.07 218387_s_at PGLS 19p13.2 2.07 212891_s_at GADD45GIP1 19p13.13 2.07 203023_at HSPC111 5q35.2 2.07 212846_at KIAA0179 21q22.3 2.07 229872_s_at LOC440667 /// LOC440669 /// 1q21.1 2.07 LOC440688 222444_at ARMCX3 Xq21.33-q22.2 2.07 200792_at XRCC6 22q13.2-q13.31 2.07 200750_s_at RAN 12q24.3 2.07 201620_at MBTPS1 16|16q24 2.07 205684_s_at C9orf55 9p22.1 2.06 213694_at RSBN1 1p13.2 2.06 226382_at LOC283070 10p14 2.06 210580_x_at SULT1A3 /// SULT1A4 16p11.2 2.06 227224_at RALGPS2 1q25.2 2.06 200809_x_at RPL12 9q34 2.06 201567_s_at GOLGA4 3p22-p21.3 2.06 212040_at TGOLN2 2p11.2 2.06 202300_at HBXIP 1p13.3 2.06 200726_at PPP1CC 12q24.1-q24.2 2.06 213016_at BBX 3q13.1 2.06 225225_at — 15 2.05 228106_at FLJ20280 4p15.32 2.05 213294_at FLJ38348 2p22.2 2.05 202642_s_at TRRAP 7q21.2-q22.1 2.05 211529_x_at HLA-G 6p21.3 2.05 225866_at BXDC1 6q21 2.05 228173_at GNAS 20q13.2-q13.3 2.05 200692_s_at HSPA9B 5q31.1 2.05 201361_at MGC5508 11q12.2 2.05 200825_s_at HYOU1 11q23.1-q23.3 2.05 208648_at VCP 9p13.3 2.05 224587_at PC4 5p13.3 2.05 200062_s_at RPL30 8q22 2.05 203143_s_at KIAA0040 1q24-25 2.05 1559942_at — 07 2.04 224502_s_at KIAA1191 5q35.2 2.04 225472_at BAT4 6p21.3 2.04 218543_s_at PARP12 7q34 2.04 201051_at ANP32A 15q22.3-q23 2.04 225581_s_at MRPL50 9q31.1 2.04 205042_at GNE 9p13.2 2.04 207585_s_at RPL36AL 14q21 2.04 221230_s_at ARID4B 1q42.1-q43 2.04 212179_at C6orf111 6q16.3 2.04 217848_s_at PP 10q11.1-q24 2.04 1556285_s_at PPA2 4q25 2.04 200910_at CCT3 1q23 2.04 212815_at ASCC3 6q16 2.04 213567_at — 03 2.03 208773_s_at ANKHD1 /// MASK-BP3 5q31.2 /// 5q31.3 2.03 209199_s_at MEF2C 5q14 2.03 217492_s_at PTENP1 9p21 2.03 227421_at C21orf57 21q22.3 2.03 202466_at POLS 5p15 2.03 200992_at IPO7 11p15.4 2.03 225235_at TSPAN17 5q35.3 2.03 218041_x_at SLC38A2 12q 2.03 228370_at SNRPN 15q11.2 2.03 225932_s_at HNRPA2B1 7p15 2.03 224591_at HP1BP3 1p36.12 2.03 202621_at IRF3 19q13.3-q13.4 2.03 223436_s_at MGC11134 11q13.1 2.02 218422_s_at C13orf10 13q31.1 2.02 221452_s_at TMEM14B 6p25.1-p23 2.02 233746_x_at SERF2 /// HYPK 15q15.3 2.02 202336_s_at PAM 5q14-q21 2.02 226589_at FLJ38482 4q32.3 2.02 212721_at SFRS12 5q12.3 2.02 226413_at LOC400027 12q12 2.02 212117_at RHOQ 2p21 2.02 225158_at GFM1 3q25.1-q26.2 2.02 203983_at TSNAX 1q42.1 2.02 209067_s_at HNRPDL 4q13-q21 2.02 218084_x_at FXYD5 19q12-q13.1 2.02 217752_s_at CNDP2 18q22.3 2.02 202302_s_at FLJ11021 12q24.31 2.01 235775_at DKFZp762A217 12q21.31 2.01 231850_x_at KIAA1712 4q34 2.01 209358_at TAF11 6p21.31 2.01 209610_s_at SLC1A4 2p15-p13 2.01 218034_at TTC11 7q22.1 2.01 218674_at FLJ13611 5q12.3 2.01 225116_at HIPK2 7q32-q34 2.01 208891_at DUSP6 12q22-q23 2.01 205596_s_at SMURF2 17q22-q23 2.01 201011_at RPN1 3q21.3 2.01 225397_at MGC20481 15q15.1 2.01 222708_s_at STX17 9q31.1 2.01 217950_at NOSIP 19q13.33 2.00 226773_at — 04 2.00 218501_at ARHGEF3 3p21-p13 2.00 200030_s_at SLC25A3 12q23 2.00 213440_at RAB1A 2p14 2.00 224879_at C9orf123 9p24.1 2.00 223288_at USP38 04 2.00 230792_at FLJ31204 Xp11.1 2.00 212953_x_at CALR 19p13.3-p13.2 2.00 202001_s_at NDUFA6 22q13.2-q13.31 2.00 229146_at C7orf31 7p15.3 2.00 228972_at — 17 2.00 225995_x_at MGC52000 2q14.1 2.00 221775_x_at RPL22 1p36.3-p36.2 2.00 217880_at CDC27 17q12-17q23.2 1.99 218356_at FTSJ2 7p22 1.99 214661_s_at C4orf9 4p16.3 1.99 223190_s_at MLL5 7q22.1 1.99 224566_at TncRNA 11q13.1 1.99 225120_at PURB 7p13 1.99 208127_s_at SOCS5 2p21 1.99 203697_at FRZB 2qter 1.99 228084_at — 04 1.99 208619_at DDB1 11q12-q13 1.99 218703_at SEC22L2 3q21.1 1.99 223106_at TMEM14C 6p24.1 1.99 203646_at FDX1 11q22 1.98 206332_s_at IFI16 1q22 1.98 203216_s_at MYO6 6q13 1.98 239735_at — 05 1.98 214459_x_at HLA-C 6p21.3 1.98 233759_s_at KIAA1387 2p16.1 1.98 235587_at LOC202781 7q36.3 1.98 231839_at 2′-PDE 3p14.3 1.98 213214_x_at ACTG1 17q25 1.98 203837_at MAP3K5 6q22.33 1.98 208929_x_at RPL13 16q24.3|17p11.2 1.98 200777_s_at BZW1 2q33 1.98 208763_s_at TSC22D3 Xq22.3 1.98 215157_x_at PABPC1 8q22.2-q23 1.97 208051_s_at PAIP1 5p12 1.97 214736_s_at ADD1 4p16.3 1.97 218395_at ACTR6 12q23.1 1.97 202170_s_at AASDHPPT 11q22 1.97 225768_at NR1D2 3p24.2 1.97 204258_at CHD1 5q15-q21 1.97 207318_s_at CDC2L5 7p13 1.97 217834_s_at SYNCRIP 6q14-q15 1.97 225136_at PLEKHA2 8p11.23 1.97 226979_at MAP3K2 2q14.3 1.97 238465_at MGC33648 5q11.2 1.97 201359_at COPB 11p15.2 1.97 220367_s_at SAP130 2q14.3 1.97 209265_s_at METTL3 14q11.1 1.97 213730_x_at TCF3 19p13.3 1.97 208308_s_at GPI 19q13.1 1.97 226115_at AHCTF1 1q44 1.97 209023_s_at STAG2 Xq25 1.97 225706_at GLCCI1 7p21.3 1.96 209180_at RABGGTB 1p31 1.96 203804_s_at CROP 17q21.33 1.96 224621_at — 22q11.21 1.96 40225_at GAK 4p16 1.96 209200_at MEF2C 5q14 1.96 223474_at C14orf4 14q24.3 1.96 208946_s_at BECN1 17q21 1.96 201055_s_at HNRPA0 5q31 1.96 224718_at SLC25A29 14q32.2 1.96 218259_at MKL2 16p13.12 1.96 201960_s_at MYCBP2 13q22 1.96 201061_s_at STOM 9q34.1 1.96 212601_at ZZEF1 17p13.2 1.96 212099_at RHOB 2p24 1.96 236125_at DKFZp586I1420 7p15.1 1.96 202371_at TCEAL4 Xq22.2 1.96 200086_s_at COX4I1 16q22-qter 1.96 227455_at C6orf136 6p21.33 1.95 206342_x_at IDS Xq28 1.95 202957_at HCLS1 3q13 1.95 223423_at GPR160 3q26.2-q27 1.95 200705_s_at EEF1B2 2q33-q34 1.95 224516_s_at CXXC5 5q31.2 1.95 208948_s_at STAU 20q13.1 1.95 210211_s_at HSPCA 14q32.33 1.95 224889_at FOXO3A 6q21 1.95 210649_s_at ARID1A 1p35.3 1.95 222550_at ARMC1 8q13.1 1.95 224129_s_at LOC84661 2p22.3 1.95 201152_s_at MBNL1 3q25 1.95 222998_at MAF1 8q24.3 1.95 205072_s_at XRCC4 5q13-q14 1.95 233124_s_at ECHDC1 6q22.33 1.95 213390_at C19orf7 19q13.32 1.94 212648_at DHX29 5q11.2 1.94 201863_at FAM32A 19pter-p13.3 1.94 218226_s_at NDUFB4 3q13.33 1.94 224331_s_at MRPL36 5p15.3 1.94 201273_s_at SRP9 1q42.12 1.94 222199_s_at BIN3 8p21.3 1.94 203359_s_at MYCBP 1p33-p32.2 1.94 224617_at — 09 1.94 201857_at ZFR 5p13.3 1.94 202745_at USP8 15q21.2 1.94 218166_s_at HBXAP 11q13.5 1.94 202160_at CREBBP 16p13.3 1.93 203569_s_at OFD1 Xp22.2-p22.3 1.93 211271_x_at PTBP1 19p13.3 1.93 201345_s_at UBE2D2 5q31.2 1.93 213366_x_at ATP5C1 10p15.1 1.93 217887_s_at EPS15 1p32 1.93 214730_s_at GLG1 16q22-q23 1.93 206513_at AIM2 1q22 1.93 226251_at — 02 1.93 231035_s_at OTUD1 10p12.31 1.93 203284_s_at HS2ST1 1p31.1-p22.1 1.93 208722_s_at ANAPC5 12q24.31 1.93 39582_at CYLD 16q12-q13 1.93 1567214_a_at PNN 14q21.1 1.93 202031_s_at WIPI-2 7p22.1 1.93 217730_at PP1201 2p24.3-p24.1 1.93 201197_at AMD1 6q21-q22 1.93 222621_at DNAJC1 10p12.31 1.93 202653_s_at 7-Mar 2q24.2 1.93 217900_at IARS2 1q41 1.93 239377_at MGC11102 11q13.1 1.93 201463_s_at TALDO1 11p15.5-p15.4 1.93 221532_s_at WDR61 15q25.1 1.92 228095_at PHF14 7p21.3 1.92 209580_s_at MBD4 3q21-q22 1.92 215023_s_at PEX1 7q21-q22 1.92 211986_at AHNAK 11q12.2 1.92 225686_at FAM33A 17q23.2 1.92 207127_s_at HNRPH3 10q22 1.92 201603_at PPP1R12A 12q15-q21 1.92 202318_s_at SENP6 6q13-q14.3 1.92 219363_s_at MTERFD1 8q22.1 1.91 224831_at CPEB4 5q21 1.91 200088_x_at RPL12 9q34 1.91 212053_at KIAA0251 16p13.11 1.91 223396_at TMEM60 7q11.23 1.91 226694_at PALM2-AKAP2 9q31-q33 1.91 221488_s_at C6orf82 6pter-p21.31 1.91 206240_s_at ZNF136 19p13.2-p13.12 1.91 202042_at HARS 5q31.3 1.91 220525_s_at AUP1 2p13 1.91 218403_at P53CSV 12q24.31 1.91 1554089_s_at SBDS /// SBDSP 7q11.21 /// 7q11.23 1.91 208826_x_at HINT1 5q31.2 1.90 205480_s_at UGP2 2p14-p13 1.90 201748_s_at SAFB 19p13.3-p13.2 1.90 215780_s_at SET /// LOC389168 9q34 /// 3q25.31 1.90 212635_at TNPO1 5q13.2 1.90 213879_at SUMO2 17q25.1 1.90 203613_s_at NDUFB6 9p21.1 1.90 213503_x_at ANXA2 15q21-q22 1.90 213086_s_at CSNK1A1 5q32 1.90 224967_at UGCG 9q31 1.90 217958_at TRAPPC4 11q23.3 1.90 202424_at MAP2K2 19p13.3 1.90 208904_s_at RPS28 19p13.2 1.90 230078_at KIAA1961 5q23.3 1.90 213453_x_at GAPDH 12p13 1.90 201692_at OPRS1 9p13.3 1.90 200049_at MYST2 17q21.32 −2.12 210561_s_at WSB1 17q11.1 −2.12 1552612_at CDC42SE2 5q23.3 −2.12 63009_at SHQ1 3p13 −2.13 225673_at MYADM 19q13.42 −2.13 212370_x_at FAM21B /// LOC387680 10q11.22 /// 10q11.23 −2.13 38710_at OTUB1 11q13.1 −2.13 1566003_x_at — 16 −2.13 241490_s_at — 01 −2.13 208730_x_at RAB2 8q12.1 −2.14 232749_at RAB12 18p11.22 −2.14 207665_at ADAM21 14q24.1 −2.14 228565_at KIAA1804 1q42 −2.14 205140_at FPGT 1p31.1 −2.14 241202_at GALNT10 5q33.2 −2.15 225897_at MARCKS 6q22.2 −2.15 203363_s_at KIAA0652 11p11.2 −2.15 218091_at HRB 2q36.3 −2.15 1557810_at CCT5 5p15.2 −2.15 234143_at — 05 −2.16 224630_at C2orf30 2p16.3 −2.16 226198_at TOM1L2 17p11.2 −2.16 209136_s_at USP10 16q24.1 −2.16 223602_at USP30 12q24.11 −2.16 212625_at STX10 19p13.13 −2.16 201494_at PRCP 11q14 −2.17 217540_at — 03 −2.17 207408_at SLC22A14 3p21.3 −2.17 202919_at PREI3 2q33.1 −2.18 218021_at DHRS4 14q11.2 −2.18 211693_at MGC27165 14q32.33 −2.18 1552632_a_at KIAA1001 17q24.2 −2.19 211754_s_at SLC25A17 22q13.2 −2.19 222699_s_at PLEKHF2 8q22.1 −2.19 209782_s_at DBP 19q13.3 −2.19 242895_x_at RNF39 6p21.3 −2.19 201830_s_at NET1 10p15 −2.20 244016_at — — −2.20 230648_at LOC283663 15q21.3 −2.21 232066_x_at MGC21675 4p16.3 −2.21 211543_s_at GRK6 5q35 −2.21 219180_s_at PEX26 22q11.21 −2.21 47560_at LPHN1 19p13.2 −2.21 1553153_at ATP6V0D2 08 −2.21 206846_s_at HDAC6 Xp11.23 −2.22 242787_at INCENP 11q12-q13 −2.22 211416_x_at GGTLA4 20p11.1 −2.22 201647_s_at SCARB2 4q21.1 −2.22 218218_at DIP13B 12q24.1 −2.22 224560_at TIMP2 17q25 −2.22 1561683_at — 01 −2.22 228003_at RAB30 11q12-q14 −2.23 1566002_at — 16 −2.23 239960_x_at — −2.24 230592_at C1orf48 1q41 −2.24 208704_x_at APLP2 11q23-q25|11q24 −2.25 206478_at KIAA0125 14q32.33 −2.25 218582_at 5-Mar 10q23.32-q23.33 −2.25 211610_at KLF6 10p15 −2.25 229693_at LOC388335 17p13.1 −2.25 234974_at GALM 2p22.1 −2.26 213957_s_at CAP350 1p36.13-q41 −2.26 225263_at HS6ST1 2q21 −2.26 223650_s_at NRBF2 10q21.3 −2.26 1570248_at GNB1 1p36.33 −2.26 231449_at — 02 −2.27 227143_s_at BID 22q11.1 −2.27 202902_s_at CTSS 1q21 −2.27 209379_s_at KIAA1128 10q23.1 −2.27 218866_s_at POLR3K 16p13.3 −2.27 240015_at — 10p15.1 −2.27 211935_at ARL6IP 16p12-p11.2 −2.28 228240_at — 02 −2.28 202092_s_at ARL2BP 16q13 −2.28 236539_at PTPN22 1p13.3-p13.1 −2.28 228906_at CXXC6 10q21 −2.28 209882_at RIT1 1q22 −2.28 223356_s_at MTIF3 13q12.2 −2.29 243148_at TJP2 9q13-q21 −2.29 225756_at CSNK1E 22q13.1 −2.29 232264_at EDD 8q22 −2.29 218888_s_at NETO2 16q11 −2.29 235648_at ZNF567 19q13.12 −2.29 203967_at CDC6 17q21.3 −2.29 37232_at KIAA0586 14q23.1 −2.30 225042_s_at C12orf22 12q13.11-q13.12 −2.30 224405_at FCRL5 1q21 −2.30 211945_s_at ITGB1 10p11.2 −2.30 208832_at ATXN10 22q13.31 −2.30 226580_at BRMS1L 14q13.2 −2.30 205550_s_at BRE 2p23.2 −2.31 37170_at BMP2K 4q21.21 −2.31 205698_s_at MAP2K6 17q24.3 −2.31 50314_i_at C20orf27 20p13 −2.32 229465_s_at PTPRS 19p13.3 −2.32 218173_s_at WHSC1L1 8p11.2 −2.32 211068_x_at FAM21C /// LOC439973 10q11.1 /// 10q11.23 −2.32 222657_s_at FLJ11011 8q21.11 −2.33 219675_s_at UXS1 2q12.2 −2.33 232471_at MYO1E 15q21-q22 −2.33 1557276_at — 06 −2.33 211630_s_at GSS 20q11.2 −2.33 212293_at HIPK1 1p13.2 −2.33 1559052_s_at PAK2 3q29 −2.33 210284_s_at MAP3K7IP2 6q25.1-q25.3 −2.34 231106_at LOC255326 10q11.22 −2.34 52741_at C14orf172 14q32.32 −2.34 205745_x_at ADAM17 2p25 −2.35 221006_s_at SNX27 1q21.3 −2.35 211074_at FOLR1 11q13.3-q14.1 −2.36 200928_s_at RAB14 9q32-q34.11 −2.36 238675_x_at MGC23908 1p32.3 −2.37 204903_x_at APG4B 2q37.3 −2.38 244764_at HIVEP3 1p34 −2.38 1554167_a_at GOLGA7 8p11.21 −2.38 227035_x_at LOC441212 7p14.3 −2.39 213340_s_at KIAA0495 1p36.32 −2.40 235479_at CPEB2 4p15.33 −2.40 238437_at LOC390980 19q13.43 −2.40 226354_at LACTB 15q22.1 −2.40 1562476_at RAD51 15q15.1 −2.40 224555_x_at IL1F7 2q12-q14.1 −2.40 211734_s_at FCER1A 1q23 −2.40 208540_x_at S100A11 1q21 −2.40 208733_at RAB2 8q12.1 −2.40 227125_at IFNAR2 21q22.1 −2.41 239084_at SNAP29 22q11.21 −2.41 201050_at PLD3 19q13.2 −2.41 204565_at THEM2 6p22.2 −2.41 37793_r_at RAD51L3 17q11 −2.41 223228_at LDOC1L 22q13.31 −2.41 1568678_s_at FGFR1OP 6q27 −2.42 1554344_s_at AQP12B /// AQP12A 2q37.3 −2.42 206468_s_at KIAA0859 1q24-q25.3 −2.42 1557818_x_at — 13 −2.42 215521_at PHC3 3q26.2 −2.42 210935_s_at WDR1 4p16.1 −2.42 226887_at HSPA14 10p13 −2.43 202535_at FADD 11q13.3 −2.43 1568696_at ARMETL1 10p14 −2.43 235258_at DCP2 5q22.2 −2.44 219095_at PLA2G4B 15q11.2-q21.3 −2.44 218725_at SLC25A22 11p15.5 −2.45 204624_at ATP7B 13q14.3 −2.45 238035_at SP3 2q31 −2.45 244022_at FNDC3B 3q26.31 −2.45 205372_at PLAG1 8q12 −2.46 222441_x_at C20orf45 20q13.32 −2.46 215528_at — 02 −2.46 238795_at C10orf18 10p15.1 −2.46 241996_at — 10 −2.46 1553678_a_at ITGB1 10p11.2 −2.47 215032_at RREB1 6p25 −2.47 1562256_at NALP1 17p13 −2.48 224886_at LOC339123 16p13.3 −2.48 214582_at PDE3B 11p15.1 −2.48 209964_s_at ATXN7 3p21.1-p12 −2.48 222207_x_at — 07 −2.48 215177_s_at ITGA6 2q31.1 −2.48 230082_at LRRFIP2 3p22.3 −2.48 232440_at ZDHHC13 11p15.1 −2.48 218871_x_at GALNACT-2 10q11.21 −2.48 203266_s_at MAP2K4 17p11.2 −2.48 202805_s_at ABCC1 16p13.1 −2.49 222955_s_at FAM45B /// FAM45A Xq25 /// 10q25 −2.49 223354_x_at C2orf33 2q36.3 −2.50 215758_x_at ZNF505 19p12 −2.50 227338_at LOC440983 3q25.1 −2.50 212835_at KIAA0157 10q26.13 −2.51 202510_s_at TNFAIP2 14q32 −2.51 217499_x_at OR7E37P 13q14.11 −2.51 201775_s_at KIAA0494 1pter-p22.1 −2.52 206194_at HOXC4 /// FLJ12825 12q13.3 /// 12q13.13 −2.52 1557193_at PTPN2 18p11.3-p11.2 −2.52 243913_at MYOM2 8p23.3 −2.53 212311_at KIAA0746 4p15.2 −2.53 36907_at MVK 12q24 −2.53 220701_at — 14 −2.53 242876_at — 01 −2.54 238075_at — 11 −2.54 230376_at GTF2A2 15q22.2 −2.54 219648_at DSU 2q35 −2.54 213002_at MARCKS 6q22.2 −2.54 212314_at KIAA0746 4p15.2 −2.55 202749_at WRB 21q22.3 −2.55 229933_at C1orf74 1q32.2 −2.55 213106_at ATP8A1 4p14-p12 −2.55 222732_at TRIM39 6p21.3 −2.56 222235_s_at GALNACT-2 10q11.21 −2.56 1553535_a_at RANGAP1 22q13 −2.57 1553239_at FLJ30707 13q14.3 −2.57 218297_at C10orf97 10p13 −2.57 218043_s_at AZI2 3p24.1 −2.57 224377_s_at RAB18 10p12.1 −2.57 203883_s_at RAB11FIP2 10q26.11 −2.58 1561571_at LOC389183 3q27.3 −2.58 220865_s_at TPRT 10p12.1 −2.58 1563772_a_at LAMA3 18q11.2 −2.58 224404_s_at FCRL5 1q21 −2.59 203158_s_at GLS 2q32-q34 −2.59 226272_at — 01 −2.59 241429_at — 10 −2.59 206218_at MAGEB2 Xp21.3 −2.61 1557986_s_at ATP6V0C /// SHMT1 16p13.3 /// 17p11.2 −2.61 241844_x_at FLJ23235 4p14 −2.61 202317_s_at UBE4B 1p36.3 −2.61 232922_s_at C20orf59 20q13.33 −2.62 223945_x_at LOC441212 7p14.3 −2.62 234464_s_at EME1 17q21.33 −2.62 232422_at LOC87769 13q32.3 −2.62 234634_at EXT1 8q24.11-q24.13 −2.63 238029_s_at SLC16A14 2q36.3 −2.63 228139_at RIPK3 14q11.2 −2.63 221419_s_at — 16 −2.63 230651_at THOC2 Xq25-q26.3 −2.64 207265_s_at KDELR3 22q13.1 −2.64 220949_s_at MGC5242 7q33 −2.64 235749_at UGCGL2 13q32.1 −2.64 206632_s_at APOBEC3B 22q13.1-q13.2 −2.65 32811_at MYO1C 17p13 −2.65 1554757_a_at INPP5A 10q26.3 −2.65 218967_s_at PTER 10p12 −2.66 211089_s_at NEK3 13q14.13 −2.66 202075_s_at PLTP 20q12-q13.1 −2.66 200709_at FKBP1A 20p13 −2.66 1556345_s_at MCCC2 5q12-q13 −2.66 229466_at LOC256273 11p15.3 −2.67 224806_at TRIM25 17q23.2 −2.67 201739_at SGK 6q23 −2.68 210001_s_at SOCS1 16p13.13 −2.69 215376_at — 08 −2.70 202894_at EPHB4 7q22 −2.70 202120_x_at AP2S1 19q13.2-q13.3 −2.70 235055_x_at MUC4 3q29 −2.71 218322_s_at ACSL5 10q25.1-q25.2 −2.71 1560386_at XPO1 2p16 −2.72 38964_r_at WAS Xp11.4-p11.21 −2.72 37425_g_at CCHCR1 6p21.3 −2.72 217975_at WBP5 Xq22.2 −2.72 219731_at FLJ34077 10q23-q24 −2.72 1555820_a_at FLJ20345 17q23.2 −2.73 243830_at — 03 −2.73 208732_at RAB2 8q12.1 −2.74 206066_s_at RAD51C 17q22-q23 −2.74 1553048_a_at PIP5K2B 17q12 −2.75 1557966_x_at MTERFD2 2q37.3 −2.75 227090_at PHF21A 11p11.2 −2.75 1558166_at MGC16275 17q25.2 −2.75 217104_at LOC400410 15q25.1 −2.75 219870_at ATF7IP2 16p13.13 −2.75 125207_x_at YDD19 /// C6orf68 /// LOC389850 13q12 /// 6q22.1 /// Xp11.3 −2.76 /// LOC440128 /// 13q12.12 215764_x_at AP2A2 11p15.5 −2.76 234609_at PRKCE 2p21 −2.76 214869_x_at GAPVD1 9q33.3 −2.77 1570360_s_at DDX3Y Yq11 −2.77 206263_at FMO4 1q23-q25 −2.77 1555916_at RPUSD3 3p25.3 −2.77 241669_x_at PRKD2 19q13.3 −2.78 38069_at CLCN7 16p13 −2.79 203851_at IGFBP6 12q13 −2.80 235366_at ZNF10 12q24.33 −2.80 202881_x_at — 06 −2.80 225585_at RAP2A 13q34 −2.81 1552863_a_at CACNG6 19q13.4 −2.81 230769_at FLJ37099 1p13.2-p13.1 −2.81 204906_at RPS6KA2 6q27 −2.82 201360_at CST3 20p11.21 −2.82 221498_at SNX27 1q21.3 −2.83 1555860_x_at — 03 −2.84 238004_at PGBD2 1q44 −2.84 235882_at — 17 −2.84 226664_at TBC1D20 20p13 −2.85 1568713_a_at TBC1D1 4p14 −2.85 230448_at MGC15523 17q25.3 −2.85 218662_s_at HCAP-G 4p15.33 −2.86 243522_at SPPL3 12q24.31 −2.86 230042_at — 21 −2.86 206686_at PDK1 2q31.1 −2.87 226571_s_at PTPRS 19p13.3 −2.87 1568887_at — 01 −2.88 239349_at C1QTNF7 4p16-p15 −2.88 225656_at EFHC1 6p12.3 −2.89 225172_at CRAMP1L 16p13.3 −2.89 203278_s_at PHF21A 11p11.2 −2.89 214706_at ZNF200 16p13.3 −2.90 213587_s_at ATP6V0E2L 7q36.1 −2.90 209474_s_at ENTPD1 10q24 −2.92 225754_at AP1G1 16q23 −2.93 1560290_at — 16 −2.94 240062_at FAM3C 7q22.1-q31.1 −2.94 1553112_s_at CDK8 13q12 −2.94 1563646_a_at MGC26979 8q22.1 −2.94 233361_at ANKRD44 2q33.1 −2.95 215946_x_at LOC91353 22q11.23 −2.95 219570_at C20orf23 20p11.23 −2.95 221590_s_at ALDH6A1 14q24.3 −2.96 202641_at ARL3 10q23.3 −2.96 210731_s_at LGALS8 1q42-q43 −2.96 217597_x_at RAB40B 17q25.3 −2.97 204079_at TPST2 22q12.1 −2.97 209766_at PRDX3 10q25-q26 −2.97 243986_at LOC144766 13q21.31 −2.98 1557586_s_at ATP6V1H 8p22-q22.3 −2.98 121_at PAX8 2q12-q14 −2.99 205197_s_at ATP7A Xq13.2-q13.3 −2.99 216253_s_at PARVB 22q13.2-q13.33 −2.99 232366_at KIAA0232 4p16.1 −2.99 235299_at — 12 −2.99 202292_x_at LYPLA2 /// LYPLA2P1 /// 1p36.12-p35.1 /// 6p21.32 −3.00 LOC388499 /// 19p13.2 238846_at TNFRSF11A 18q22.1 −3.00 231002_s_at NUP88 17p13.2 −3.01 203418_at CCNA2 4q25-q31 −3.01 1554518_at FLJ13273 4q24 −3.02 229351_at C6orf49 6p21.31 −3.02 233168_s_at SELO 22q13.33 −3.03 229821_at NBR2 17q21 −3.04 213264_at PCBP2 12q13.12-q13.13 −3.04 229637_at hSyn 12q23.3 −3.04 227885_at PRO1768 14q32.11 −3.05 1553088_a_at BCL2L11 2q13 −3.06 244357_at LOC64744 1p35.3-p34.1 −3.06 233055_at — 02 −3.06 1568408_x_at — 14 −3.07 207543_s_at P4HA1 10q21.3-q23.1 −3.07 1554582_a_at MGC50559 12p11.21 −3.07 239267_at — 09 −3.07 1560826_at — 08 −3.07 221951_at LOC283232 11p15.5 −3.09 208591_s_at PDE3B 11p15.1 −3.09 31861_at IGHMBP2 11q13.3 −3.09 211433_x_at KIAA1539 9p13.3 −3.10 214462_at SOCS6 18q22.2 −3.10 238025_at MLKL 16q22.3 −3.11 1554769_at FLJ32130 16p11.2 −3.11 214119_s_at FKBP1A 20p13 −3.12 225226_at FAM40A 1p13.3 −3.12 43934_at C11ORF4 11cen-q22.3 −3.12 209416_s_at FZR1 19p13.3 −3.12 217706_at LOC220074 11q13.4 −3.12 229835_s_at C20orf45 20q13.32 −3.13 239725_at PGAP1 2q33.1 −3.14 202403_s_at COL1A2 7q22.1 −3.14 210186_s_at FKBP1A 20p13 −3.14 237187_at — 12 −3.14 240979_at — 17 −3.15 1560981_a_at PPARA 22q12-q13.1|22q13.31 −3.17 217994_x_at CPSF3L 1p36.33 −3.17 223798_at SLC41A2 12q23.3 −3.18 219330_at VANGL1 1p11-p13.1 −3.18 1570249_x_at GNB1 1p36.33 −3.20 1557158_s_at MLL3 7q34-q36 −3.21 234575_at ZNF71 19q13.4 −3.22 1562259_at TEX9 15q21.3 −3.22 219032_x_at OPN3 1q43 −3.23 58994_at CC2D1A 19p13.12 −3.23 209467_s_at MKNK1 1p33 −3.24 239314_at LOC387921 13q13.3 −3.24 218554_s_at ASH1L 1q22 −3.25 219801_at ZNF34 8q24.3 −3.25 1557890_at — 06 −3.25 228990_at C1orf79 1p35.3 −3.26 57540_at RBKS 2p23.3 −3.26 33323_r_at SFN 1p36.11 −3.28 201029_s_at CD99 Xp22.32; Yp11.3 −3.29 212872_s_at TRFP 6p21.1 −3.30 221569_at AHI1 6q23.3 −3.31 1554471_a_at ANKRD13C 1p32.3-p31.3 −3.32 218273_s_at PPM2C 8q22.1 −3.33 230108_at ERCC6 10q11.23 −3.33 221542_s_at SPFH2 8p11.2 −3.34 206576_s_at CEACAM1 19q13.2 −3.38 219472_at MGC11266 2p23.3 −3.38 211152_s_at PRSS25 2p12 −3.38 222252_x_at UBQLN4 /// UBQLN4P 1q21 /// 3q24 −3.39 226457_at — 01 −3.39 220564_at C10orf59 10q23.31 −3.40 201028_s_at CD99 Xp22.32; Yp11.3 −3.40 217128_s_at CAMK1G 1q32-q41 −3.42 1569629_x_at LOC389906 Xp22.33 −3.43 240423_at — 7p15.2 −3.46 1553905_at CXorf22 Xp21.1 −3.46 218068_s_at ZNF672 1q44 −3.47 228034_x_at FLJ20308 17p11.2 −3.48 227986_at ZNF343 20p13 −3.48 210779_x_at SIP1 14q13 −3.48 235089_at FBXL20 17q12 −3.48 242159_at — 12 −3.48 230333_at SAT Xp22.1 −3.50 37965_at PARVB 22q13.2-q13.33 −3.55 242041_at CSPP 8q13.2 −3.57 1555288_s_at FBF1 17q25.1 −3.57 243440_at — 02 −3.58 241380_at FLJ41603 5q32 −3.59 241906_at ZNF15L1 7q −3.61 200659_s_at PHB 17q21 −3.63 221999_at VRK3 19q13 −3.65 207425_s_at 9-Sep 17q25 −3.66 209280_at MRC2 17q23.3 −3.67 1553002_at DEFB105A 08 −3.70 227683_x_at NUDT4 01 −3.71 221681_s_at DSPP 4q21.3 −3.75 215481_s_at PEX5 12p13.3 −3.75 242956_at IDH1 2q33.3 −3.76 216491_x_at IGHM 14q32.33 −3.78 224097_s_at F11R 1q21.2-q21.3 −3.81 206150_at TNFRSF7 12p13 −3.82 217111_at AMACR 5p13.2-q11.1 −3.83 225105_at LOC387882 12q23.3 −3.84 211918_x_at PAPPA2 1q23-q25 −3.85 221080_s_at FAM31C 19p13.3 −3.86 223107_s_at PS1D 1p35.2 −3.86 227337_at ANKRD37 4q35.1 −3.91 201801_s_at SLC29A1 6p21.1-p21.2 −3.92 1559691_at NDUFS1 2q33-q34 −3.94 209710_at GATA2 3q21.3 −3.95 1561391_at STAU2 8q13-q21.1 −3.95 234231_at LOC197350 16p13.3 −3.96 1557944_s_at CTNND1 11q11 −3.97 203307_at GNL1 6p21.3 −3.97 229191_at TBCD 17q25.3 −4.00 209626_s_at OSBPL3 7p15 −4.02 220066_at CARD15 16q21 −4.02 217462_at C11orf9 11q12-q13.1 −4.07 203003_at MEF2D 1q12-q23 −4.07 229250_at TPCN2 11q13.3 −4.08 201849_at BNIP3 10q26.3 −4.10 222951_s_at ANKRD5 20pter-q11.23 −4.11 207300_s_at F7 13q34 −4.11 227046_at SLC39A11 17q24.3-q25.1 −4.18 220036_s_at LMBR1L 12q13.12 −4.21 202563_at C14orf1 14q24.3 −4.30 203093_s_at TIMM44 19p13.3-p13.2 −4.35 215410_at PMS2L1 /// PMS2L2 /// PMS2L5 7q22.1 /// 7q11-q22 /// −4.36 /// PMS2L11 /// LOC442593 7q11.23 229906_at ARMC7 17q25.1 −4.41 213249_at FBXL7 5p15.1 −4.50 233891_at — −4.52 219125_s_at LOC55974 1q22 −4.64 1553793_a_at KIAA1109 4q27 −4.65 1570454_at EIF4EBP2 10q21-q22 −4.70 215949_x_at IGHM 14q32.33 −4.71 202837_at TRAFD1 12q −4.75 211159_s_at PPP2R5D 6p21.1 −4.83 230491_at — 12 −4.94 216846_at IGLJ3 22q11.1-q11.2 −5.35 234381_at IGLC2 22q11.2 −5.94 Note: + Score means higher expression in monoclonal gammopathy of undetermined significance than in normal plasma cell.

TABLE 3 Genes significantly expressed between monoclonal gammopathy of undetermined significance and multiple myeloma. SAM Probe Set Symbol Map Location Score 1565951_s_at CHML 1q42-qter 4.86 235117_at LOC494143 2p16 4.50 208910_s_at C1QBP 17p13.3 4.45 214773_x_at TIPRL 1q23.2 4.32 204071_s_at TOPORS 9p21 4.28 203198_at CDK9 9q34.1 4.26 209424_s_at AMACR 5p13.2-q11.1 4.22 1557765_at LOC340109 5p14.1 4.14 201486_at RCN2 15q23 4.13 203886_s_at FBLN2 3p25.1 4.11 226760_at LOC203411 Xp22.13 4.10 221727_at PC4 5p13.3 /// 8p23.1 4.06 202475_at NIFIE14 19q13.1 4.00 219029_at FLJ21657 5p12 3.99 1555225_at C1orf43 1q21.2 3.99 1555226_s_at C1orf43 1q21.2 3.97 214484_s_at OPRS1 9p13.3 3.96 1560316_s_at GLCCI1 7p21.3 3.94 201873_s_at ABCE1 4q31 3.86 201461_s_at MAPKAPK2 1q32 3.85 228620_at PRKRA 2q31.2 3.80 212846_at KIAA0179 21q22.3 3.80 225260_s_at MRPL32 7p14 3.77 215050_x_at MAPKAPK2 1q32 3.74 207396_s_at ALG3 3q27.1 3.73 217398_x_at GAPDH 12p13 3.73 223223_at ARV1 1q42.2 3.73 234672_s_at TMEM48 1p32.3 3.70 210480_s_at MYO6 6q13 3.70 223046_at EGLN1 1q42.1 3.70 235103_at MAN2A1 5q21-q22 3.69 223804_s_at THUMPD3 3p25.3 3.69 219481_at TTC13 1q42.2 3.68 225805_at HNRPU 1q44 3.66 230795_at HIST1H4D 6p21.3 3.66 227109_at CYP2R1 11p15.2 3.66 226784_at TWISTNB 7p21.1 3.66 224713_at MKI67IP 2q14.3 3.63 229804_x_at CBWD1 9p24.3 /// 2q14.1 /// 9q13 3.62 232392_at SFRS3 6p21 3.61 224654_at DDX21 10q21 /// 8p23.3 3.61 208490_x_at HIST1H2BF 6p21.3 3.60 222673_x_at TMEM57 1p36.11 /// Xq26.3 3.60 235384_at NUDT19 19q13.11 3.60 224436_s_at NIPSNAP3A 9q31.1 3.59 213188_s_at MINA 3q11.2 3.59 228324_at C9orf41 9q21.13 3.59 212789_at hCAP-D3 11q25 3.57 229785_at KRIT1 7q21-q22 3.55 217777_s_at HSPC121 15q22.2 3.54 202069_s_at IDH3A 15q25.1-q25.2 3.54 224714_at MKI67IP 2q14.3 3.53 226752_at UNQ1912 5q21.1 3.53 1569454_a_at LOC283352 12q24.33 3.52 203235_at THOP1 19q13.3 3.49 233952_s_at ZNF295 21q22.3 3.48 225699_at LOC285958 7p13 3.47 225734_at FBXO22 15q23 3.44 1558254_s_at SRPK2 7q22-q31.1 3.44 212417_at SCAMP1 5q13.3-q14.1 3.44 244631_at LOC389834 chr2 3.44 218837_s_at UBE2D4 7p13 3.43 225223_at SMAD5 5q31 3.43 212907_at SLC30A1 1q32-q41 3.42 1558755_x_at ZNF440L 19p13.2 3.42 225317_at ACBD6 1q25.2-q25.3 3.42 212536_at ATP11B 3q27 3.41 223649_s_at CGI-69 17q12 3.39 229846_s_at MAPKAP1 9q33.3 3.39 222204_s_at RRN3 16p12 3.38 235039_x_at LIN9 1q42.12 3.38 227211_at PHF19 9q33.2 3.38 218052_s_at ATP13A1 19p13.11 3.36 230766_at — chr21 3.36 204928_s_at SLC10A3 Xq28 3.36 200730_s_at PTP4A1 6q12 3.36 203622_s_at LOC56902 2p14 3.35 222280_at GAPDS 19q13.1 3.35 202422_s_at ACSL4 Xq22.3-q23 3.35 201177_s_at UBA2 19q12 3.35 203216_s_at MYO6 6q13 3.35 218009_s_at PRC1 15q26.1 3.34 1564651_at LOC221710 6p24.1 3.34 201326_at CCT6A 7p11.2 3.33 212574_x_at C19orf6 19p13.3 3.33 204900_x_at SAP30 4q34.1 3.32 238761_at MED28 4p16 3.32 218270_at MRPL24 1q21-q22 3.31 222794_x_at PAPD1 10p11.23 3.31 203480_s_at HSHIN1 4q31.21 3.31 221156_x_at CCPG1 15q21.1 3.30 200910_at CCT3 1q23 3.30 1555790_a_at ZFPL 19q13.41 /// 4q32.3 3.29 228366_at PPA2 4q25 3.29 202904_s_at LSM5 7p14.3 3.29 230560_at STXBP6 14q12 3.27 244103_at C1orf55 1q42.12 3.26 231530_s_at C11orf1 11q13-q22 3.26 208965_s_at IFI16 1q22 3.25 201824_at RNF14 5q23.3-q31.1 3.25 201458_s_at BUB3 10q26 3.25 222147_s_at ACTR5 20q11.23 3.25 1555730_a_at CFL1 11q13 3.25 226558_at ANKRD20B 2q11.1 3.24 201485_s_at RCN2 15q23 3.24 211747_s_at LSM5 7p14.3 3.24 227246_at — chr4 3.23 204602_at DKK1 10q11.2 3.23 235109_at ZBED3 5q13.3 3.22 221207_s_at NBEA 13q13 3.22 223073_at HIATL1 9q22.32 3.22 203360_s_at MYCBP 1p33-p32.2 3.21 207508_at ATP5G3 2q31.1 3.21 225625_at MGC90512 12q24.11 3.21 228822_s_at USP16 21q22.11 3.21 227124_at — chr6 3.18 200692_s_at HSPA9B 5q31.1 3.18 203203_s_at HRB2 12q21.1 3.18 201456_s_at BUB3 10q26 3.18 201595_s_at LEREPO4 2q32.1 3.17 212038_s_at VDAC1 5q31 3.17 209147_s_at PPAP2A 5q11 3.17 208308_s_at GPI 19q13.1 3.17 218027_at MRPL15 8q11.2-q13 3.17 201013_s_at PAICS 4pter-q21 3.17 224619_at CASC4 15q15.3 3.16 218073_s_at TMEM48 1p32.3 3.16 202541_at SCYE1 4q24 3.16 225580_at MRPL50 9q31.1 3.15 211070_x_at DB1 2q12-q21 3.15 213355_at ST3GAL6 3q12.1 3.15 235032_at DNAJA5 5p13.2 3.14 207564_x_at OGT Xq13 3.14 202708_s_at HIST2H2BE 1q21-q23 3.14 215071_s_at HIST1H2AC 6p21.3 3.13 203560_at GGH 8q12.3 3.12 214290_s_at HIST2H2AA 1q21.2 3.11 226193_x_at CBWD1 9p24.3 3.11 225361_x_at LOC159090 Xq26.3 3.11 227288_at — 5q12.3 3.10 200737_at PGK1 Xq13 3.10 219366_at AVEN 15q13.1 3.10 221669_s_at ACAD8 11q25 3.10 209398_at HIST1H1C 6p21.3 3.09 239609_s_at LOC254531 15q14 3.09 200968_s_at PPIB 15q21-q22 3.08 230298_at LOC153364 5q14.3 3.08 221677_s_at DONSON 21q22.1 3.08 221652_s_at C12orf11 12p11.23 3.06 214931_s_at SRPK2 7q22-q31.1 3.06 209100_at IFRD2 3p21.3 3.06 226493_at KCTD18 2q33.1 3.06 201890_at RRM2 2p25-p24 3.06 210802_s_at HSA9761 5q11-q14 3.05 203362_s_at MAD2L1 4q27 3.05 227669_at DKFZPS64B167 1q24 3.05 1553698_a_at C1orf96 1q42.13 3.04 202169_s_at AASDHPPT 11q22 3.04 213427_at RPP40 6p25.1 3.04 225028_at LOC550643 Xq11.1 3.03 214214_s_at C1QBP 17p13.3 3.03 1554455_at LINS1 15q26.3 3.03 218527_at APTX 9p13.3 3.03 221020_s_at MFTC 8q22.3 3.03 212133_at NIPA2 15q11.2 3.02 204176_at KLHL20 1q24.1-q24.3 3.02 235274_at — chr15 3.02 203044_at CHSY1 15q26.3 3.02 208523_x_at HIST1H2BI 6p21.3 3.02 203182_s_at SRPK2 7q22-q31.1 3.01 212416_at SCAMP1 5q13.3-q14.1 3.01 225633_at DPY19L3 19q13.11 3.01 228190_at — chr1 3.01 204905_s_at EEF1E1 6p24.3-p25.1 3.01 229299_at FLJ30596 5p13.2 3.01 208669_s_at CRI1 15q21.1-q21.2 3.01 64900_at CHST5 16q22.3 /// 3p21.2 3.00 1560982_at — chr16 3.00 201577_at NME1 17q21.3 2.99 206562_s_at CSNK1A1 5q32 2.98 231130_at FKBP7 2q31.2 2.98 211934_x_at GANAB 11q12.3 2.97 219675_s_at UXS1 2q12.2 2.97 218668_s_at RAP2C Xq25 2.97 228561_at CDC37L1 chr9 2.97 242214_at RPS27A 2p16 /// 1q31.2 /// 6q21 2.97 235532_at — chr1 2.96 215030_at GRSF1 4q13 2.96 203427_at ASF1A 6q22.31 2.95 218280_x_at HIST2H2AA 1q21.2 2.95 218962_s_at FLJ13576 7q31.32 2.95 224824_at FAM36A 1q44 2.95 235168_at — chr1 2.94 225737_s_at FBXO22 15q23 2.94 227418_at KIAA1826 11q22 2.94 217356_s_at PGK1 Xq13 2.92 1558692_at MGC31963 1q22 2.92 201479_at DKC1 Xq28 2.92 220980_s_at ADPGK 15q24.1 2.91 208864_s_at TXN 9q31 2.91 219200_at MGC5297 5p15.3-p15.2 2.90 218988_at SLC35E3 12q15 2.89 223686_at TPK1 7q34-q35 2.89 241734_at SRFBP1 5q23.1 2.89 218590_at PEO1 10q23.3-24.3 2.88 202024_at ASNA1 19q13.3 2.88 212297_at ATP13A3 3q29 2.88 222825_at CGI-77 8q21.3 2.88 209267_s_at SLC39A8 4q22-q24 2.88 213453_x_at GAPDH 12p13 2.88 220346_at MTHFD2L 4q13.3 2.87 224723_x_at LOC401397 7q31.1 2.87 1558801_at — 2.87 204444_at KIF11 10q24.1 2.87 1556151_at CDA08 16q12.1 2.86 218386_x_at USP16 21q22.11 2.86 224883_at PLDN 15q21.1 2.85 220954_s_at PILRB 7q22.1 2.85 217790_s_at SSR3 3q25.31 2.85 222154_s_at DNAPTP6 2q33.1 2.85 201317_s_at PSMA2 7p14.1 2.84 210370_s_at LY9 1q21.3-q22 2.83 217898_at C15orf24 15q14 2.83 219628_at WIG1 3q26.3-q27 2.83 229235_at — chr16 2.82 210275_s_at ZA20D2 9q13-q21 2.81 229491_at LOC133308 4q24 2.81 209161_at PRPF4 9q31-q33 2.81 218512_at WDR12 2q33.2 2.80 202430_s_at PLSCR1 3q23 2.80 221568_s_at LIN7C 11p14 2.78 220850_at MORC1 3q13 2.78 209773_s_at RRM2 2p25-p24 2.77 201817_at UBE3C 7q36.3 2.77 235205_at LOC346887 8q23.1 2.77 238762_at MTHFD2L 4q13.3 2.77 219003_s_at MANEA 6q16.1 2.77 213485_s_at ABCC10 6p21.1 2.76 219177_at BXDC2 5p13.2 2.76 231297_at DOT1L 19p13.3 2.76 242201_at — chr7 2.76 223264_at MESDC1 15q13 2.76 224523_s_at MGC4308 3q12.1 2.76 217933_s_at LAP3 4p15.32 2.75 203452_at B3GAT3 11q12.3 2.75 201115_at POLD2 7p13 2.75 220175_s_at CBWD1 9p24.3 /// 2q14.1 /// 9q13 /// 2.74 9q21.13 235907_at TMEM33 4p13 2.74 213626_at CBR4 4q32.3 2.74 224391_s_at CSE-C 11q24 2.74 219787_s_at ECT2 3q26.1-q26.2 2.73 202070_s_at IDH3A 15q25.1-q25.2 2.73 235581_at — chr7 2.72 200994_at IPO7 11p15.4 2.72 222428_s_at LARS 5q32 2.71 236193_at HIST1H2BC 6p21.3 2.70 222412_s_at SSR3 3q25.31 2.70 235159_at FLJ11000 7q33 2.70 202591_s_at SSBP1 7q34 2.69 223470_at PIGM 1q23.2 2.68 218568_at MULK 7q34 2.68 204244_s_at ASK 7q21.3 2.67 208775_at XPO1 2p16 2.67 205386_s_at MDM2 12q14.3-q15 2.67 205361_s_at PFDN4 20q13.2 2.65 225904_at C1orf96 1q42.13 2.64 230005_at DKFZp313A2432 11p14.2 2.64 209628_at NXT2 Xq23 2.64 225916_at ZNF131 5p12-p11 2.63 202396_at TCERG1 5q31 2.63 1554321_a_at NFS1 20q11.22 2.63 224875_at FLJ37562 5q31.1 2.63 208828_at POLE3 9q33 2.63 212279_at MAC30 17q11.2 2.63 224903_at CIRH1A 16q22.1 2.63 230177_at — chr5 2.62 229551_x_at ZNF367 9q22 2.62 1556194_a_at — chr4 2.62 217856_at RBM8A 1q12 2.61 229082_at KENAE 5q13.2 2.60 223243_s_at C1orf22 1q24-q25 2.59 209426_s_at AMACR 5p13.2-q11.1 2.59 223261_at POLK 5q13 2.58 228559_at — chr16 2.58 222163_s_at SPATA5L1 15q21.1 2.58 201312_s_at SH3BGRL Xq13.3 2.58 201624_at DARS 2q21.3 2.58 208967_s_at AK2 1p34 2.57 1555815_a_at L3MBTL2 22q13.31-q13.33 2.56 214835_s_at SUCLG2 3p14.1 2.56 223077_at TMOD3 15q21.1-q21.2 2.55 1555948_s_at C9orf10 9q22.31 2.55 201251_at PKM2 15q22 2.54 223180_s_at C18orf55 18q22.3 2.53 218397_at FANCL 2p16.1 2.53 215954_s_at C19orf29 19p13.3 2.52 225385_s_at HNRPLL 2p22.1 2.52 214218_s_at XIST Xq13.2 −2.50 219966_x_at BANP 16q24 −2.52 213340_s_at KIAA0495 1p36.32 −2.52 225688_s_at PHLDB2 3q13.2 −2.52 202459_s_at LPIN2 18p11.31 −2.53 214679_x_at GNA11 19p13.3 −2.54 219049_at ChGn 8p21.3 −2.55 239292_at — 3p24.1 −2.55 204164_at SIPA1 11q13 −2.56 224693_at C20orf108 20q13.31 −2.56 1570243_at — −2.56 209158_s_at PSCD2 19q13.3 −2.56 206150_at TNFRSF7 12p13 −2.56 224588_at XIST Xq13.2 −2.57 227917_at — −2.57 243738_at NMNAT3 3q23 −2.57 223769_x_at HYI 1p34.2 −2.57 242104_at — 22q13.2 −2.57 213183_s_at CDKN1C 11p15.5 −2.59 241435_at ETS1 11q23.3 −2.59 228139_at RIPK3 14q11.2 −2.59 208472_at ZNFN1A4 12q13 −2.60 236494_x_at — chr1 −2.61 241685_x_at — chr5 −2.62 215785_s_at CYFIP2 5q33.3 −2.62 219593_at SLC15A3 11q12.2 −2.62 213940_s_at FNBP1 9q34 −2.62 219062_s_at ZCCHC2 18q21.33 −2.64 226497_s_at FLT1 13q12 −2.64 220758_s_at ROBO4 11q24.2 −2.64 239694_at TRIM7 5q35.3 −2.64 205277_at PRDM2 1p36 −2.65 220066_at CARD15 16q21 −2.66 210347_s_at BCL11A 2p16.1 −2.67 208779_x_at DDR1 6p21.3 −2.68 232693_s_at ZNF395 8p21.1 −2.70 223681_s_at INADL 1p31.3 −2.70 1558794_at — −2.70 243795_s_at — chr2 −2.71 232511_at RANBP2L1 2q13 −2.71 216894_x_at CDKN1C 11p15.5 −2.72 212589_at SCP2 1p32 −2.72 214677_x_at IGL 22q11.1-q11.2 /// 22q11.2 −2.72 1555888_at EDD 8q22 −2.73 212230_at PPAP2B 1pter-p22.1 −2.74 203823_at RGS3 9q32 −2.74 204912_at IL10RA 11q23 −2.74 242451_x_at INO80 15q15.1 −2.74 209619_at CD74 5q32 −2.75 213944_x_at GNA11 19p13.3 −2.76 205898_at CX3CR1 3p21|3p21.3 −2.76 221651_x_at IGKC 2p12 −2.76 226459_at PIK3AP1 10q24.1 −2.76 203206_at FAM53B 10q26.13 −2.76 206695_x_at ZNF43 19p13.1-p12 −2.77 241944_x_at TNFRSF1A 12p13.2 −2.78 202897_at PTPNS1 20p13 −2.80 227331_at LOC283337 12q13.13 −2.81 239809_at KLF7 2q32 −2.81 231989_s_at LOC23117 16p12.2 −2.81 36742_at TRIM15 6p21.3 −2.81 220377_at C14orf110 14q32.33 −2.82 227396_at — chr11 −2.83 1566780_at — X −2.84 210749_x_at DDR1 6p21.3 −2.85 208456_s_at RRAS2 11p15.2 −2.85 205482_x_at SNX15 11q12 −2.86 202460_s_at LPIN2 18p11.31 −2.86 218032_at SNN 16p13 −2.87 239283_at TMED5 1pter-q31.3 −2.89 235099_at CKLFSF8 3p23 −2.89 203313_s_at TGIF 18p11.3 −2.89 1556839_s_at SPTBN5 15q21 −2.91 224795_x_at IGKC 2p12 −2.91 201938_at CDK2AP1 12q24.31 −2.91 1007_s_at DDR1 6p21.3 −2.91 220989_s_at AMN 14q32.3 −2.92 221671_x_at IGKC 2p12 −2.92 228951_at FLJ10815 16q21 −2.92 205514_at ZNF415 19q13.42 −2.93 203708_at PDE4B 1p31 −2.93 1565358_at RARA 17q21 −2.94 204798_at MYB 6q22-q23 −2.94 210162_s_at NFATC1 18q23 −2.95 215949_x_at IGHM 14q32.33 −2.96 213350_at RPS11 19q13.3 −2.98 210715_s_at SPINT2 19q13.1 −2.98 213642_at — chr1 −2.99 232072_at ASAHL 4q21.1 −3.00 211230_s_at PIK3CD 1p36.2 −3.00 212590_at RRAS2 11p15.2 −3.02 234753_x_at — chr18 −3.02 49329_at KLHL22 22q11.21 −3.03 210356_x_at MS4A1 11q12 −3.04 208315_x_at TRAF3 14q32.32 −3.05 230253_at SCUBE3 6p21.3 −3.05 225051_at EPB41 1p33-p32 −3.06 1558075_at LOC339047 16p12.3 −3.06 217016_x_at FLJ23172 3q26.31 −3.06 204257_at FADS3 11q12-q13.1 −3.07 221969_at PAX5 9p13 −3.08 227778_at KIAA1833 8q24.3 −3.08 217418_x_at MS4A1 11q12 −3.09 223415_at RPP25 15q24.1 −3.09 214041_x_at RPL37A 2q35 −3.09 34210_at CD52 1p36 −3.10 218546_at C1orf115 1q41 −3.11 219371_s_at KLF2 19p13.13-p13.11 −3.11 209808_x_at ING1 13q34 −3.12 224590_at XIST Xq13.2 −3.13 221479_s_at BNIP3L 8p21 −3.13 221558_s_at LEF1 4q23-q25 −3.16 211430_s_at IGH 14q32.33 −3.17 239516_at LYPLAL1 1q41 −3.19 201811_x_at SH3BP5 3p24.3 −3.20 216563_at ANKRD12 18p11.22 −3.21 1554636_at — chr19 −3.23 224562_at WASF2 1p36.11-p34.3 −3.23 235081_x_at TRIM65 17q25.1 −3.25 1555779_a_at CD79A 19q13.2 −3.26 202724_s_at FOXO1A 13q14.1 −3.27 215671_at PDE4B 1p31 −3.30 202615_at GNAQ 9q21 −3.31 242472_x_at FNBP4 11p11.2 −3.31 221011_s_at LBH 2p23.1 −3.31 1569906_s_at PHF20 20q11.22-q11.23 −3.32 212226_s_at PPAP2B 1pter-p22.1 −3.33 218502_s_at TRPS1 8q24.12 −3.34 1564310_a_at PARP15 3q21.1 −3.35 212288_at FNBP1 9q34 −3.37 222329_x_at — chr4 −3.38 230807_at MGC20983 19p13.2 −3.39 204588_s_at SLC7A7 14q11.2 −3.42 223467_at RASD1 17p11.2 −3.44 211697_x_at LOC56902 2p14 −3.45 1560754_at CKLFSF7 3p23 −3.46 244654_at MYO1G 7p13-p11.2 −3.46 220068_at VPREB3 22q11.23|22q11 −3.49 228592_at MS4A1 11q12 −3.52 209795_at CD69 12p13-p12 −3.58 224493_x_at C18orf45 18q11.2 −3.63 217022_s_at IGHA1 14q32.33 −3.64 1553185_at RASEF 9q21.32 −3.64 243895_x_at — chr18 −3.66 209116_x_at HBB 11p15.5 −3.68 221943_x_at RPL38 17q23-q25 −3.69 1553186_x_at RASEF 9q21.32 −3.79 1553575_at — chr5 −3.84 217232_x_at HBB 11p15.5 −3.89 225955_at METRNL 17q25.3 −3.94 234381_at IGLC2 22q11.2 −3.95 203037_s_at MTSS1 8p22 −3.96 211696_x_at HBB 11p15.5 −4.02 216491_x_at IGHM 14q32.33 −4.25 210450_at LOC90925 14q32.33 −4.31 211699_x_at HBA1 16p13.3 −4.86 214414_x_at HBA2 16p13.3 −5.01 217414_x_at HBA2 16p13.3 −5.02 204018_x_at HBA1 16p13.3 −5.06 209458_x_at HBA1 16p13.3 −5.08 211745_x_at HBA1 16p13.3 −5.15 Note: + Score means higher expression in MM than in MGUS.

In another embodiment of the present invention there is provided a method of predicting clinical outcome and survival of an individual by classification of disease into subsets based on genomic signature specific for the disease and its precursor state, identified by gene expression profiling as discussed supra, where the data obtained is subjected to significance analysis of microarray (SAM), unsupervised hierarchical cluster analysis and supervised colorgram analyses on Log2-transformed signal calls intensity values of the significance analysis of microarray-defined genes. Preferably, the disease state is multiple myeloma and the precursor state is monoclonal gammopathy of undetermined significance or smoldering multiple myeloma. Specifically, the cases of multiple myeloma clustering with cases of monoclonal gammopathy of undetermined significance are classified as monoclonal gammopathy of undetermined significance-like multiple myeloma and may have a favorable clinical outcome and survival. Additionally, the cases of monoclonal gammopathy of undetermined significance clustering with multiple myeloma cases are classified as multiple myeloma-like monoclonal gammopathy of undetermined significance and may have a high rate of conversion to multiple myeloma and thus poor clinical outcome and survival.

In yet, another embodiment of the present invention there is a method of relating specific genomic signatures of a disease to its molecular classification to predict the progression and evolution of the disease from its precursor state. Preferably, the disease is multiple myeloma and the precursor state is monoclonal gammopathy of undetermined significance or smoldering multiple myeloma. In general, the molecular classification of multiple myeloma constitutes either the CD-1 high-risk disease or the CD-2 low-risk disease. CD-1 high-risk disease is characterized by spiked expression of MMSET and MAF/MAFB and PROLIFERATION signature. CD-2 low-risk disease is characterized by HYPERDIPLOIDY, LOW BONE DISEASE and CCND1/CCND3 translocations. Specifically, the cases of multiple myeloma bearing monoclonal gammopathy of undetermined significance-like genomic signature constitute the molecular characteristics of the low-risk CD-2 disease and may have evolved from the precursor state.

In still yet another embodiment of the present invention there is a method of predicting clinical outcome and patient survival in patients suffering from multiple myeloma based on correlating genomic signatures of multiple myeloma with changes in gene copy number and progression of the disease. Generally, the changes in gene copy number may involve gain/amplification and/or loss/deletion of genetic material in any human chromosome. Specifically, the fluorescent in situ hybridization defined-amplification of chromosome 1q21 is absent in monoclonal gammopathy of undetermined significance, and is present in smoldering multiple myeloma patients associated with higher risk conversion to multiple myeloma, and its presence in multiple myeloma confers shorter survival.

In still yet another embodiment of the present invention there is a method of selecting treatment for an individual diagnosed with a disease, based on the specific genomic signature for said disease. Specifically, the individual with a genomic signature of multiple myeloma-like monoclonal gammopathy of undetermined significance (MM-L MGUS) may be selected for aggressive treatment and an individual with a genomic signature of monoclonal gammopathy of undetermined significance-like multiple myeloma (MGUS-like MM) may be selected for less aggressive forms of treatment.

As used herein, the term, “a” or “an” may mean one or more. As used herein in the claim(s), when used in conjunction with the word “comprising”, the words “a” or “an” may mean one or more than one. As used herein “another” or “other” may mean at least a second or more of the same or different claim element or components thereof.

The following examples are given for the purpose of illustrating various embodiments of the invention and are not meant to limit the present invention in any fashion. One skilled in the art will appreciate readily that the present invention is well adapted to carry out the objects and obtain the ends and advantages mentioned, as well as those objects, ends and advantages inherent herein. Changes therein and other uses which are encompassed within the spirit of the invention as defined by the scope of the claims will occur to those skilled in the art.

EXAMPLE 1 Study Subjects

The International Myeloma Working Group criteria were used to classify the patients as having monoclonal gammopathy of undetermined significance, smoldering multiple myeloma and symptomatic multiple myeloma. For a diagnosis of monoclonal gammopathy of undetermined significance, levels of monoclonal protein could not exceed 30 g/L and of bone marrow infiltration with plasma cells 10%; there could not be any evidence of related organ or tissue impairment defined as hypercalcemia, renal impairment, anemia or bone lesions attributed to plasma cell proliferation. In the case of smoldering multiple myeloma, related organ or tissue impairment had to be absent but levels of bone marrow plasmacytosis exceeded 10% and of monoclonal protein 30 g/L.

The analysis described utilized samples from 22 healthy donors; 72 patients with monoclonal gammopathy of undetermined significance (MGUS) (n=56) or smoldering multiple myeloma (SMM) (n=16) or multiple myeloma with a monoclonal gammopathy of undetermined significance history (n=16) and 351 patients treated with Total Therapy 2 (TT2), a tandem transplant for symptomatic or progressive multiple myeloma (Barlogie B, et al., 2006). The test set comprised 214 patients with multiple myeloma enrolled in Total Therapy 3 (TT3) and 20 patients surviving greater than 10 years after treatment with Total Therapy 1 (TT1) (Barlogie B, et al., 2006). Table 4 lists laboratory parameters for the monoclonal gammopathy of undetermined significance/smoldering multiple myeloma (at diagnosis or progression to multiple myeloma) and for multiple myeloma (prior to initiation of therapy). In the case of monoclonal gammopathy of undetermined significance/smoldering multiple myeloma, data were also retrieved from records of the referring institution. Thirty-two subjects of the monoclonal gammopathy of undetermined significance/smoldering multiple myeloma group had been enrolled in a prospective observational Southwest Oncology Group study (SWOG 0210), which called for clinical staging with bone marrow biopsy, skeletal survey and magnetic resonance imaging at initial registration, and follow-up at 3-6 mo intervals.

TABLE 4 Patient characteristics of MGUS, SMM, MM from MGUS, TT1, TT2 and TT3 at diagnosis^(a).

Age ≧ 65 yr 36 225 63 5 23 30 .001

White race 84 92 25 80 29 89 <.001

B2M 11 17 64 45 49 57 <.001* ≧3.0 mg/liter

Creatinine 2 0 7 5 11 8 NS ≧2.0 mg/dl

Albumin 2 8 6 30 14 14 .049 <3.5 g/dl

Cytogenetic 0 0 6 20 24 31 <.001 abnromalities

MRI ≧ 1 0 25 25 62 72 73 <.001 ^(a)Fisher exact test, otherwise chi-square test. # Values represent the percentage of cases with the specified variable

Plasma cells were purified from bone marrow aspirates of 72 patients, 56 with monoclonal gammopathy of undetermined significance and 16 with smoldering multiple myeloma (together termed “monoclonal gammopathy of undetermined significance”). Group A (19 monoclonal gammopathy of undetermined significance and 5 smoldering multiple myeloma) with documented stable disease parameters for at least 2.5 yr (median 4.3 yr, mean 5.5 yr; range, 2.5 yr to 14.5 yr) was used to identify monoclonal gammopathy of undetermined significance-genes; smoldering multiple myeloma cases included in this group had less than 20% plasma cells at latest follow-up. For Group B (25 monoclonal gammopathy of undetermined significance and 7 smoldering multiple myeloma), the most recent follow-up was less than 2.5 yr (median 1.5 yr, mean 2.0 yr; range 0 yr to 7.3 yr). Group C consisted of 16 patients with multiple myeloma converted from monoclonal gammopathy of undetermined significance (n=12) or smoldering multiple myeloma (n=4), the criteria of which pertained for at least 1 yr (median 4.5, mean 6.2; range, 1.1 yr to 19 yr).

EXAMPLE 2 Sample Processing and Molecular Analyses

Plasma cell isolation, total RNA extraction, complementary RNA synthesis and hybridizations to Affymetrix U133Plus2.0 microarrays were performed as described (Zhan F, et al., 2006). Significance Analysis of Microarray (Tusher V, et al., 2001) with a false discovery rate of 0.1% was performed to identify genes uniquely expressed in monoclonal gammopathy of undetermined significance by comparing half of the monoclonal gammopathy of undetermined significance cases (n=24) with normal plasma cells cases (n=22) and 351 multiple myeloma cases. Unsupervised hierarchical (Eisen M, et al., 1998) and supervised (Golub T R, et al., 1999) cluster analysis was employed on Log2-transformed signal calls intensity values of 52 significance analysis of microarray-defined genes.

Plasma cell isolation, total RNA extraction, complementary RNA synthesis and hybridizations to Affymetrix U133Plus2.0 microarrays were performed as described previously (Zhan F, et al., 2006). Differences between monoclonal gammopathy of undetermined significance (n=24; comprising group A) and normal plasma cells (n=22) were determined by first filtering out all genes with an absent detection call in greater than half of these samples or a Chi-square value of greater than >3.84. Significance analysis of microarray (Tusher V, et al., 2001), with a false discovery rate of 1% was then applied to 9,935 probe sets. A total of 2,864 genes probe sets were differentially expressed between the two groups. Genes making up a myeloid cell and/or normal plasma cell contamination signature were further subtracted. The contamination signature, including 5,351 probe sets, was defined by the comparison of 95 multiple myeloma contaminated by myeloid cells and/or normal plasma cells to 256 multiple myeloma without contamination (significance analysis of microarray false discovery rate<1%) (Zhan F, et al., 2006).

This lead to the identification of 2,181 genes probe sets, with 1,736 over-expressed and 444 under-expressed in monoclonal gammopathy of undetermined significance relative to normal plasma cells (refer to Table 2). By using the same strategy, a total of 458 genes with 161 over- and 297 under-expressed in monoclonal gammopathy of undetermined significance were found differentially expressed in a comparison between monoclonal gammopathy of undetermined significance (n=24; group A) and multiple myeloma (n=351) (Table 3). Using significance analysis of microarray-intersect analysis 52 genes were found to be significantly differentially expressed in both comparisons (refer to Table 5). Unsupervised hierarchical cluster analysis and supervised colorgram analyses were employed on Log2-transformed signal calls intensity values of the 52 significance analysis of microarray-defined genes.

TABLE 5 Fifty-two significance analysis of microarray-defined genes are differentially expressed in normal plasma cells, monoclonal gammopathy of undetermined significance, and multiple myeloma^(a).

201486_at RCN2 unknown; calcium 2.48 1.55 4.13 1.63 binding, ER lumen

212846_at KIAA0179 unknown; nucleolar 2.07 1.30 3.80 1.48 protein

222673_x_at TMEM57 unknown; 3.19 1.65 3.60 1.63 transmembrane protein

225223_at SMAD5 gene transcription 3.12 1.70 3.43 1.41

203216_s_at MYO6 recessive actin-based 1.98 1.57 3.35 1.91 motor

200910_at CCT3 molecular chaperone 2.04 1.34 3.30 1.60

221207_(')s_at NBEA protein kinase A 3.42 1.83 3.22 2.49 regulator

212038_s_at VDAC1 ion channel for 1.62 1.56 3.17 1.42 cytochrome c

201013_s_at PA1CS DNA synthesis 2.81 1.43 3.17 1.45

215071_s_at HIST1H2AC chromosome 3.47 3.62 3.13 1.97 organization and biogenesis

219366_at AVEN anti-apoptosis 2.63 1.76 3.10 1.47

221652_s_at C12orf11 unknown; sarcoma 2.07 1.37 3.06 1.57 antigen

214214_s_at C1QBP immunity 2.27 1.45 3.03 1.47

218280_x_at HIST2H2AA chromosome 4.24 4.76 2.95 1.92 organization and biogenesis

208864_s_at TXN redox reactions 2.90 1.68 2.91 1.51

222825_at OTUD6B unknown 2.66 1.35 2.88 1.40

217898_at C15orf24 unknown 2.35 1.70 2.83 1.33

213485_s_at ABCC10 ATP-dependent efflux 3.17 1.51 2.76 1.34 pump; multidrug resistance pump

222428_s_at LARS protein synthesis 3.64 1.68 2.71 1.32

204244_s_aat ASK cell cycle 3.25 1.77 2.67 1.37

202396_at TCERG1 gene transcription 3.85 1.62 2.63 1.32

213340_s_at KIAA0495 unknown −2.40 0.78 2.52 0.75

228139_at RIPK3 cell signaling −2.63 0.74 −2.59 0.77

232511_at RANDP2L1 Nuclear improt 2.07 1.54 −2.71 0.64

219371_s_at KLF2 gene transcription 3.81 1.78 −3.11 0.66

215671_at PDE4B drug metabolism 2.07 1.53 −3.30 0.59

219675_s_at UXS1 glycosaminoglycan −2.33 0.76 2.97 1.35 biosynthesis ^(a)genes are ordered based on the significance of microarray score in the MGUS v. MM comparison. ^(b)A positive significance analysis of microarray score in the MGUS v. NPC column indicates the gene expression is higher in MGUS relative to normal plasma cels. ^(c)A positive significance analysis of microarray score in the MM v. MGUS column indicates the gene is higher in MM relative to MGUS.

Approximately one-third of CD138-enriched cells from newly diagnosed cases in training and test sets had a myeloid cell gene expression signature attributable to contamination of the selected fraction with cells of this lineage. Such cases were not included in a previous molecular classification of multiple myeloma, as their bone marrow plasmacytosis was lower and survival superior. Bone marrow plasma cells proportions of subjects with monoclonal gammopathy of undetermined significance and normal donors are also low and therefore could also have myeloid cell contamination (Zhan F, et al., 2006). However, no significant difference was observed in the proportions with myeloid signature in monoclonal gammopathy of undetermined significance-like and non-monoclonal gammopathy of undetermined significance-like multiple myeloma of the training set (24% v. 28%; P=0.56), suggesting that the monoclonal gammopathy of undetermined significance-like designation was not an artifact of the cell purification procedure. For interphase fluorescent in situ hybridization analysis of abnormalities of chromosome 1q21 and 13q14, procedures described were employed (Hanamura 1, et al., 2006).

EXAMPLE 3 Statistical Analyses

The Kaplan-Meier Method was used to estimate overall survival, with group comparisons made using the log-rank test. Overall survival was defined from the date of registration until death from any cause; survivors were censored at the time of last contact. Univariate and multivariate analyses of prognostic factors were carried out using Cox regression. The cumulative incidence of Cox regression was estimated using the method outlined in Gooley et al., and compared using the log-rank test.

EXAMPLE 4 Clinical, Laboratory and Molecular Features in Subjects with Monoclonal Gammopathy of Undetermined Significance, Smoldering Multiple Myeloma and Multiple Myeloma

As expected, patients with multiple myeloma had features of greater tumor burden and aggressiveness than subjects with monoclonal gammopathy of undetermined significance or smoldering multiple myeloma (refer to Table 4). Thus, there were higher proportions of patients in the multiple myeloma group with elevations of beta-2-microglobulin (B2M), C-reactive protein (CRP), lactate dehydrogenase (LDH), creatinine and bone marrow plasmacytosis as well as lower levels of hemoglobin and albumin. Focal lesions were absent in all subjects with monoclonal gammopathy of undetermined significance but were present in 17% of smoldering multiple myeloma and 80% of patients with multiple myeloma, 59% of whom had at least 3 focal lesions. Cytogenetic abnormalities were absent in all monoclonal gammopathy of undetermined significance and smoldering multiple myeloma cases and present in one-third of patients with multiple myeloma. Patients with multiple myeloma evolved from monoclonal gammopathy of undetermined significance tended to be older and, as a group, had higher hemoglobin levels, fewer cytogenetic abnormalities, lower levels of marrow plasmacytosis and fewer magnetic resonance imaging lesions than patients with multiple myeloma, in whom a prior monoclonal gammopathy of undetermined significance/smoldering multiple myeloma history was not documented.

In a recent report on a validated molecular classification of multiple myeloma into seven disease subtypes, “spiked” expression of MMSET and AF/MAFB and PROLIFERATION signatures together constituted high-risk disease, whereas HYPERDIPLOIDY, LOW BONE DISEASE and CCND1/CCND3 translocations represented low-risk multiple myeloma. When applied to this training set, PROLIFERATION, MMSET and CCND-1 signatures were under-represented and LB and CCND-2 signatures over-represented in monoclonal gammopathy of undetermined significance/smoldering multiple myeloma; in contrast, HYPERDIPLOIDY and MAF/MAFB signatures were noted in similar frequencies in monoclonal gammopathy of undetermined significance and smoldering multiple myeloma relative to monoclonal gammopathy of undetermined significance-evolved multiple myeloma and multiple myeloma (refer to Table 1).

EXAMPLE 5 Identifying Genes Uniquely Dysregulated in Plasma Cells of Monoclonal Gammopathy of Undetermined Significance in the Context of Plasma Cells of Normal Subjects and Patients with Multiple Myeloma

Significance analysis of microarray intersection analyses identified 52 genes with differential expression levels across normal plasma cells, monoclonal gammopathy of undetermined significance and multiple myeloma; these were involved in cell cycle control, DNA synthesis, chromosome assembly, nuclear protein import, gene transcription, cell aging, cell signaling, metabolism, energy production, ion transport, reactive oxygen metabolism, drug resistance and programmed cell death/apoptosis (refer to Table 5). Of the 52 genes, 41 exhibited a progressive increase in expression levels along the transition from normal plasma cells to monoclonal gammopathy of undetermined significance to multiple myeloma, while 4 exhibited a progressive reduction in expression from normal plasma cells to monoclonal gammopathy of undetermined significance to multiple myeloma; 6 genes had higher and 1 gene lower expression levels in monoclonal gammopathy of undetermined significance relative to both normal plasma cells and multiple myeloma.

The differential expression of the 52 genes in the 22 normal plasma cells and 24 monoclonal gammopathy of undetermined significance cases was visualized through unsupervised hierarchical clustering (FIG. 1): 2 major branches were identified, one containing all but 2 of the monoclonal gammopathy of undetermined significance cases and the other comprising all but 2 of the normal plasma cells samples. When applied to the 72 cases of monoclonal gammopathy of undetermined significance or monoclonal gammopathy of undetermined significance-evolved multiple myeloma and the 351 multiple myeloma cases of the training group, the sample dendrogram produced 2 major branches, one containing 56 of 72 (78%) monoclonal gammopathy of undetermined significance cases together with 99 of 351 (28%) multiple myeloma cases including 7 of 16 (43%) of monoclonal gammopathy of undetermined significance-evolved multiple myeloma monoclonal gammopathy of undetermined significance; the second branch comprised 252 of the 351 (72%) of multiple myeloma and only 16 of 72 (22%) cases of monoclonal gammopathy of undetermined significance/smoldering multiple myeloma (FIG. 2). Multiple myeloma cases on the first branch were designated monoclonal gammopathy of undetermined significance-like multiple myeloma (MGUS-L MM), while those on the second branch were termed non-monoclonal gammopathy of undetermined significance-like (non-MGUS-L MM); the monoclonal gammopathy of undetermined significance cases on the second branch were designated multiple myeloma-like (MM-L MGUS). Supervised cluster analysis was used to provide a visualization of the differential expression of the 52 genes across the groups described along with normal plasma cells and human myeloma cell lines (MMCL) (FIG. 3). Normal plasma cells and multiple myeloma cell lines represent the extremes of benign and malignant plasma cells, and their plasma cells gene expression profiling signatures are consistent with this extreme divergence. Box plots of the expression of select genes are shown in FIG. 4. TNFSF7/CD27, KIAA0495 and CARD15 genes were progressively down-regulated, whereas CCT3, VDAC1 and DKC1 genes were progressively up-regulated in the transition from normal plasma cells to multiple myeloma cell lines. HIST1H2AC, HIST1H2AC and NBEA were representative of genes showing an increase from normal plasma cells to the monoclonal gammopathy of undetermined significance-like multiple myeloma with a reduction in expression seen in the non-monoclonal gammopathy of undetermined significance-like multiple myeloma and especially in multiple myeloma cell lines.

EXAMPLE 6 Relating Monoclonal Gammopathy of Undetermined Significance-Like and Non Monoclonal Gammopathy of Undetermined Significance-Like Signatures to Previously Identified Molecular Classes of Multiple Myeloma

Whether there were differences in the distribution of molecular subgroups in the monoclonal gammopathy of undetermined significance-like multiple myeloma and non-monoclonal gammopathy of undetermined significance-like multiple myeloma cases was determined next. Of the 351 cases of multiple myeloma used in the current analysis, 95 had been excluded because of myeloid expression signature from the molecular classification schema described previously (see Patients and Methods, Zhan F, et al., 2006) leaving 76 monoclonal gammopathy of undetermined significance-like and 180 non-monoclonal gammopathy of undetermined significance-like multiple myeloma for the 7-subtype molecular model (Table 6). A PROLIFERATION signature was absent in all monoclonal gammopathy of undetermined significance-like multiple myeloma and present in 29 (16%) of the non-monoclonal gammopathy of undetermined significance-like multiple myeloma (P<0.001) HYPERDIPLOIDY was less frequent in monoclonal gammopathy of undetermined significance-like multiple myeloma (5% v. 34%, P<0.001); CCND1-1 and CCND1-2 groups (characterized by spiked expression of CCND1 or CCND3) were more common in monoclonal gammopathy of undetermined significance-like multiple myeloma than in non-monoclonal gammopathy of undetermined significance-like multiple myeloma (15% v. 6%; P=0.038 for CCND1-1 and 47% v. 4%; p<0.001 for CCND1-2).

TABLE 6 Molecular subgroup distribution in monoclonal gammopathy of undetermined significance-like multiple myeloma and non-monoclonal gammopathy of undetermined significance-like multiple myeloma in the training set.

PROLIFERATION 0 16 <.001

MMSET 12 19 NS

CCND1-1 15 6 0.038

MAF 10 8 NS

EXAMPLE 7 A Monoclonal Gammopathy of Undetermined Significance-Like Signature is Associated with Favorable Clinical Characteristics and Superior Survival in Spite of Lower Incidence of Complete Remission

Relative to non-monoclonal gammopathy of undetermined significance-like multiple myeloma, monoclonal gammopathy of undetermined significance-like multiple myeloma was characterized by lower frequencies of elevated B2M (>3 mg/L) (33% v. 56%; P<0.001), CA (17% v. 42%; P<0.001), high-risk molecular subgroups (PROLIFERATION, MMSET or MAF) (22% v. 43%, P=0.001), elevated lactate dehydrogenase (LDH) (>upper limit of normal, ULN) (12% v. 26%; P=0.005) and bone marrow plasmacytosis (>30%) (56% vs 70%; P=0.0012) (Table 7).

TABLE 7 Patient characteristics in monoclonal gammopathy of undetermined significance- like and non-monoclonal gammopathy of undetermined significance- like multiple myeloma in the training set

B2M ≧ 3.0 mg/liter 33 56 <.001

Subgroups with poor progno- 22 43 0.001 sis (Proliferation/MMSET/ MAF)

Plasma cells (Aspirate) > 30% 56 70 0.018 Variables with P > = .02: age, race, sex, isotype, creatinine, hemoglobin, MRI lesions, c-reactive protein and albumin Despite a lower frequency of complete and near-complete remission in monoclonal gammopathy of undetermined significance-like multiple myeloma (P=0.006), such patients enjoyed a superior 5-yr survival than the remainder with non-monoclonal gammopathy of undetermined significance-like multiple myeloma (76% v. 59%, P=0.009) (FIG. 5A). Inter-phase fluorescence in situ hybridization-defined gains/amplification of 1q21 (amp1q21) in multiple myeloma tumor cells is associated with an inferior survival (Hanamura I, et al., 2006). When examined in 253 of the 351 cases, amp1q21 was less frequent in monoclonal gammopathy of undetermined significance-like multiple myeloma relative to non-monoclonal gammopathy of undetermined significance-like multiple myeloma (35% v. 49%, P=0.04). Importantly, the negative prognostic impact of amp1q21 was only seen in the non-monoclonal gammopathy of undetermined significance-like multiple myeloma group, whose 5-yr survival was 44% in the presence and 73% in the absence of amp1q21 (P=0.0008) and, thus, similar to monoclonal gammopathy of undetermined significance-like multiple myeloma (FIG. 5B). Chromosome 13 deletion, tested in 325 patients, was present with similar frequencies in monoclonal gammopathy of undetermined significance-like and non-monoclonal gammopathy of undetermined significance-like multiple myeloma (52% v. 49%, P=0.5) and was not linked to survival in either group.

On multivariate analysis, the non-monoclonal gammopathy of undetermined significance-like designation was an independent high-risk feature in addition to high-risk molecular subgroup designation, low albumin, high lactate dehydrogenase and presence of focal lesions on magnetic resonance imaging examination (Table 8).

TABLE 8 Multivariate proportional hazards analysis for overall survival in test set (N = 234^(†))

% HR 95% CI P

LDH ≧ upper limit off normal 21 2.27 1.35, 3.82 0.002

Albumin < 3.5 g/dL 16 1.92 1.09, 3.37 0.024

^(†)Total of 234 cases with complete data on all variables were available for the analysis. Only significant variables are shown.

EXAMPLE 8 Monoclonal Gammopathy of Undetermined Significance-Like Multiple Myeloma Signature is Linked to Low Risk Clinical and Molecular Characteristics in Separate Test Cohort of Newly Diagnosed Multiple Myeloma

When applied to plasma cells of a separate cohort of 213 newly diagnosed multiple myeloma enrolled in Total Therapy 3 and evaluated in the context of the 72 cases of monoclonal gammopathy of undetermined significance and monoclonal gammopathy of undetermined significance-evolved multiple myeloma, two major branches in the sample dendrogram were noted in this test set: 58 of 72 (80%) monoclonal gammopathy of undetermined significance clustered together with 55 (26%) of 213 multiple myeloma cases (FIG. 6). As with the 28% of monoclonal gammopathy of undetermined significance-like multiple myeloma in the training group, the monoclonal gammopathy of undetermined significance-like multiple myeloma group of the test set comprised fewer cases with elevated beta-2-microglobulin (42% v 63%; P=0.006) and lactate dehydrogenase (7% v. 23%, P=0.012), cytogenetic abnormalities (16% v. 36%, P=0.006) and high-risk genetic subgroups (19% v. 41%, P=0.018) (Table 9). None of the monoclonal gammopathy of undetermined significance-like multiple myeloma cases in the test set had a PROLIFERATION signature, few belonged to the MMSET group, and CCND1-1 and CCND1-2 designations predominated (Table 10).

TABLE 9 Patient characteristics in monoclonal gammopathy of undetermined significance- like and non-monoclonal gammopathy of undetermined significance- like multiple myeloma in the test set.

B2M ≧ 3.0 mg/L 42 63 0.006

LDH ≧ upper limit of normal 7 23 0.012

Variables with P > = .02: age, race, sex, isotype, creatinine, hemoglobin, magnetic resonance imaging lesions, c-reactive protein and albumin

TABLE 10 Distribution of molecular subgroups in monoclonal gammopathy off undetermined significance-like multiple myeloma and non-monoclonal gammopathy of undetermined significance-like multiple myeloma of test set.

PROLIFERATION 0 14 <.001

MMSET 3 18 <.001

CCND1-1 13 2 .003

MAF 15 9 NS

EXAMPLE 9 Long Term Survivors have an Monoclonal Gammopathy of Undetermined Significance-L Signature

Finally, unsupervised hierarchical cluster analysis of CD138-selected plasma cells of 20 patients with multiple myeloma surviving more than 10 years after initiation of Total Therapy 1 was performed, (Barlogie B, et al., 2006) together with the 72 monoclonal gammopathy of undetermined significance and the 351 newly diagnosed multiple myeloma cases in the training set (FIG. 7). The sample dendrogram had 2 main branches, one containing all monoclonal gammopathy of undetermined significance and monoclonal gammopathy of undetermined significance-like multiple myeloma and 15 of 20 (75%) of the long-term survivors (P<0.001). Expression spikes for MAF and MAFB (with CCND2 over expression), CCND1 and CCND3 were observed in the TT1 plasma cells. The presence of spikes had no influence on whether the sample was defined as being monoclonal gammopathy of undetermined significance-like versus non-monoclonal gammopathy of undetermined significance-like.

The Following References are Cited Herein:

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1. A method of gene expression profiling to identify genomic signatures specific for a disease comprising: isolating plasma cells from individuals within a population; extracting nucleic acid from said plasma cells; hybridizing said nucleic acid to a DNA microarray; and performing comparative analysis on data obtained from said hybridization, wherein said analysis identifies specific genomic signatures for said disease.
 2. The method of claim 1, wherein said genomic signature comprises: genes differentially expressed in plasma cells from a precursor form of the disease in comparison to expression of said gene(s) in normal plasma cells, and/or plasma cells from the disease.
 3. The method of claim 1, wherein said disease is multiple myeloma.
 4. The method of claim 1, wherein said disease is in its precursor form of monoclonal gammopathy of undetermined significance or smoldering multiple myeloma.
 5. The method of claim 2, wherein said genes are ABCC10, ASK, ATP11B, ATP13A3, AVEN, BCL11A, C11orf1, C12orf11, C15orf24, C1QBP, C9orf41, CARD15, CCT3, DKC1, FOXO1A, GPI, HIST1H1C, HIST1H2AC, HIST2H2AA, HIST2H2BE, HSPA9B, IPO7, KIAA0179, KIAA049, KLF2, LARS, LOC15909, LOC550643, MED28, MRPL32, MYO6, NBEA, NIFIE14, NME1, OTUD6B, PAIC, PDE4B, RANBP2L1, RCN2, RIPK3, RPL37A, SLC39A8, SMAD5, SSBP1, TCERG, TMEM57, TNFRSF7, TXN, UXS1, VDAC1, ZA20D2, and ZNF131.
 6. The method of claim 1, further comprising performing significance analysis of microarray intersection analysis and unsupervised hierarchical clustering analysis on data obtained from said hybridization, wherein said analysis classifies the subset of disease, based on the genomic signature, thereby predicting clinical outcome and survival of said individual.
 7. The method of claim 6, wherein said subset classification is monoclonal gammopathy of undetermined significance-like multiple myeloma and comprises: multiple myeloma cases that cluster with cases of monoclonal gammopathy of undetermined significance.
 8. The method of claim 6, wherein said subset classification is non-monoclonal gammopathy of undetermined significance-like multiple myeloma and comprises multiple myeloma cases that fail to cluster with cases of monoclonal gammopathy of undetermined significance.
 9. The method of claim 6, wherein said subset classification is multiple myeloma-like monoclonal gammopathy of undetermined significance and comprises monoclonal gammopathy of undetermined significance cases that cluster with multiple myeloma and predicts high risk of conversion to multiple myeloma.
 10. A method of predicting clinical outcome and patient survival in an individual diagnosed with from multiple myeloma comprising: correlating the genomic signature of multiple myeloma with amplification of chromosome 1q21; wherein said correlation predicts the clinical outcome and survival of said individual.
 11. The method of claim 10, wherein said genomic signature specific for a disease is identified by gene expression profiling; comprising: isolating plasma cells from individuals within a population extracting nucleic acid from said plasma cells; hybridizing said nucleic acid to a DNA microarray; and performing comparative analysis on data obtained from said hybridization, wherein said analysis identifies specific genomic signature for said disease.
 12. The method of claim 10, wherein said genomic signature comprises: genes differentially expressed in plasma cells from precursor form of the disease in comparison to expression of said gene(s) in normal plasma cell, and/or plasma cell from the disease.
 13. The method of claim 10, wherein said precursor form is monoclonal gammopathy of undetermined significance or smoldering multiple myeloma and the disease is multiple myeloma.
 14. The method of claim 12, wherein said genes are ABCC10, ASK, ATP11B, ATP13A3, AVEN, BCL11A, C11orf1, C12orf11, C15orf24, C1QBP, C9orf41, CARD15, CCT3, DKC1, FOXO1A, GPI, HIST1H1C, HIST1H2AC, HIST2H2AA, HIST2H2BE, HSPA9B, IPO7, KIAA0179, KIAA049, KLF2, LARS, LOC15909, LOC550643, MED28, MRPL32, MYO6, NBEA, NIFIE14, NME1, OTUD6B, PAIC, PDE4B, RANBP2L1, RCN2, RIPK3, RPL37A, SLC39A8, SMAD5, SSBP1, TCERG, TMEM57, TNFRSF7, TXN, UXS1, VDAC1, ZA20D2, and ZNF131.
 15. The method of claim 11, wherein said genomic signature is monoclonal gammopathy of undetermined significance-like multiple myeloma or non-monoclonal gammopathy of undetermined significance-like multiple myeloma or multiple myeloma-like monoclonal gammopathy of undetermined significance.
 16. The method of claim 11, wherein a combined genomic signature of monoclonal gammopathy of undetermined significance-like multiple myeloma and no amplification of chromosome 1q21 predicts superior clinical outcome and survival.
 17. The method of claim 11, wherein a combined genomic signature of non-monoclonal gammopathy of undetermined significance-like multiple myeloma and amplification of chromosome 1q21 predicts poor clinical outcome and survival.
 18. A method of selecting treatment for an individual suffering from disease comprising: isolating plasma cells from individuals within a population extracting nucleic acid from said plasma cells; hybridizing said nucleic acid to a DNA microarray; and performing comparative analysis on data obtained from said hybridization, wherein said analysis identifies specific genomic signature for said disease and is the basis for selected treatment of said disease.
 19. The method of claim 18, wherein said genomic signature comprises: genes differentially expressed in plasma cells from precursor form of the disease in comparison to expression of said gene(s) in normal plasma cell, and/or plasma cell from the disease.
 20. The method of claim 19, wherein said precursor state is monoclonal gammopathy of undetermined significance or smoldering multiple myeloma and the disease is multiple myeloma.
 21. The method of claim 19, wherein said genes are consisting of ABCC10, ASK, ATP11B, ATP13A3, AVEN, BCL11A, C11orf1, C12orf11, C15orf24, C1QBP, C9orf41, CARD15, CCT3, DKC1, FOXO1A, GPI, HIST1H1C, HIST1H2AC, HIST2H2AA, HIST2H2BE, HSPA9B, IPO7, KIAA0179, KIAA049, KLF2, LARS, LOC15909, LOC550643, MED28, MRPL32, MYO6, NBEA, NIFIE14, NME1, OTUD6B, PAIC, PDE4B, RANBP2L1, RCN2, RIPK3, RPL37A, SLC39A8, SMAD5, SSBP1, TCERG, TMEM57, TNFRSF7, TXN, UXS1, VDAC1, ZA20D2, and ZNF131.
 22. The method of claim 18, wherein said genomic signature is monoclonal gammopathy of undetermined significance-like multiple myeloma or non-monoclonal gammopathy of undetermined significance-like multiple myeloma or multiple myeloma-like monoclonal gammopathy of undetermined significance.
 23. The method of claim 18, wherein plasma cells from an individual bearing the genomic signature of multiple myeloma-like monoclonal gammopathy of undetermined significance indicates high risk and are selected for secondary prevention trials.
 24. The method of claim 18, wherein plasma cells from an individual bearing the genomic signature of monoclonal gammopathy of undetermined significance-like multiple myeloma indicates low risk and are selected for less aggressive treatment strategies. 